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Biomedical subjects

E A Clarke

Publications and source records attributed to E A Clarke.

At least 19 recordsLinked to original sources
PubMed2000

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.

Adult↗
PubMed2000

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.

Adolescent↗
PubMed2000

Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease.

The risk of lung and breast cancer is significantly increased after therapy for Hodgkin's disease (HD), but there are few data that describe the molecular profiles of these tumors. We investigated the genetic abnormalities in second primary lung (n = 19) and breast cancers (n = 19) that follow therapy for HD ("post-HD cancers") and compared these with changes observed in corresponding tumor types (57 lung and 20 breast cancers) arising in the general population ("sporadic cancers"). DNA obtained from archival tissues was examined using PCR-based analyses for loss of heterozygosity and microsatellite alterations (MAs) at several chromosomal regions, TP53 and K-ras gene mutations, and frameshift mutations at minisatellite sequences at the coding regions of several genes (TGF-betaRII, IGFIIR, BAX, hMSH6, and hMSH3). The occurrence of loss of heterozygosity at all chromosomal regions taken together and frequencies at most individual areas were similar for the post-HD and sporadic cancers for both lung and breast sites. The overall frequency of MAs in the post-HD tumors was substantially greater (lung, 2.4-fold, P = 0.004; breast, 4.2-fold, P = 0.16) than that in the respective sporadic cancers. No differences in the pattern of TP53 and K-ras mutations were detected between post-HD and sporadic cancers. No mutations were detected at the minisatellite sequences examined. MAs, which reflect widespread genomic instability, occur at greatly increased frequency in post-HD lung and breast cancers. Although the mechanisms underlying the development of increased MAs are unknown, they have been associated with immunosuppression and radiation exposure. Future research should address the role that MAs, as well as other influences, may play in the development of neoplasias that occur after therapy for HD.

Adenocarcinoma↗
PubMed1999

Can reduced imaging times be used for scintimammography?

A reduction in acquisition times from 10 to 5 min for scintimammography does not reduce the diagnostic value of the study when imaging for detection of breast lesions. The test showed an overall sensitivity of 96%, specificity of 100% and accuracy of 98% for breast lesions visualized on both 5 and 10 min acquisitions. Even if lymph node detection is the primary concern of the study, longer scan times do not increase the sensitivity of the test (40% on both 5 and 10 min). Scintimammography is poor at detecting lymph nodes (sensitivity 40%, specificity 69-82%) and is not useful for assessing lymph node involvement. A reduction in imaging times appeared to be consistent on both camera systems tested, which have very different display outputs. This would indicate that other departments may be able to reduce times on their systems without affecting the quality of the study. The detection of breast lesions was also consistent between reporters.

Breast↗
PubMed1998

Rates of disagreement in imaging interpretation in a group of community hospitals.

RATIONALE AND OBJECTIVES: Prospective studies of radiologists' interpretations of selected radiographs reported 20-40 years ago indicated error rates of 30% and higher. The authors retrospectively evaluated the interpretations of groups of radiologists and determined a range of rates of disagreement in interpretation. Quality assessment or recredentialing may add to the importance of such studies in the future. MATERIALS AND METHODS: Over a 7-year period, a team of radiologists reviewed imaging interpretations in the radiology departments of six community hospitals. Each review, which lasted about 3 days, included evaluation of the interpretations of a 3%-4% sample of the images read by the radiologists at these hospitals. Reading errors were quantitated and evaluated qualitatively. RESULTS: In a review of over 11,000 images read by 35 radiologists, the authors found a 4.4% mean rate of interpretation disagreement; only one radiologist had a mean rate above 8%. Qualitative analysis of the interpretation errors revealed a mean rate of 3.0% of errors that were considered to be below an acceptable standard of care. Radiologists whose errors included a relatively high proportion of false-positive findings tended to make relatively fewer total errors. CONCLUSION: Rates of disagreement for a broad range of studies that radiologists interpret in a community hospital setting appear to be far lower than earlier studies on selective radiographs indicated.

Diagnostic Errors↗
PubMed1998

Counting the cost of patients who do not attend nuclear medicine departments.

The mean rate of non-attendance at this hospital is 16%, with the Nuclear Medicine Department averaging 4%. Although only a small percentage, increasing demand for nuclear medicine studies has led to a need for greater efficiency to reduce financial losses. From April 1995 to March 1996, 104 patients did not attend over a range of 16 studies. We examined the types of study, patients and costs. The costs of wasted staff time, camera time and radiopharmaceutical ranged from pound sterling 24 (99Tc(m) thyroid) to pound sterling 470 (75Se cholesterol adrenal). This results in a loss equivalent to pound sterling 7258 over the year. There was no significant difference in non-attendance rates between different types of procedure, source and type of referral, or in the three age groups: children, working and retired population. Finally, we looked at cultural origins, segregating the groups into Asian and European origins based on surname. A significantly higher proportion of patients of Asian origin did not attend. This study has shown that it may be of benefit to target specific groups and tests. For example, at City Hospital, perhaps we should concentrate on our Asian community to ensure they understand fully what the study involves. It would also be worthwhile targeting the more expensive nuclear medicine studies.

Adolescent↗
PubMed1997

Risk of second malignant neoplasms among long-term survivors of testicular cancer.

BACKGROUND: We have quantified the site-specific risk of second malignant neoplasms among nearly 29,000 survivors (> or = 1 year) of testicular cancer, taking into account the histologic type of initial cancer and the primary therapy used to treat it. METHODS: The study cohort consisted of 28,843 men identified within 16 population-based tumor registries in North America and Europe; over 3300 men had survived more than 20 years. New invasive cancers were identified through a search of registry files. RESULTS: Second cancers were reported in 1406 men (observed-to-expected ratio [O/E] = 1.43; 95% confidence interval = 1.36-1.51), with statistically significant excesses noted for acute lymphoblastic leukemia (O/E = 5.20), acute nonlymphocytic leukemia (O/E = 3.07), melanoma (O/E = 1.69), non-Hodgkin's lymphoma (O/E = 1.88), and cancers of the stomach (O/E = 1.95), colon (O/E = 1.27), rectum (O/E = 1.41), pancreas (O/E = 2.21), prostate (O/E = 1.26), kidney (O/E = 1.50), bladder (O/E = 2.02), thyroid (O/E = 2.92), and connective tissue (O/E = 3.16). Overall risk was similar after seminomas (O/E = 1.42) or nonseminomatous tumors (O/E = 1.50). Risk of solid tumors increased with time since the diagnosis of testicular cancer, yielding an O/E = 1.54 (O = 369) among 20-year survivors (two-sided P for trend = .00002). Secondary leukemia was associated with both radiotherapy and chemotherapy, whereas excess cancers of the stomach, bladder, and, possibly, pancreas were associated mainly with radiotherapy. CONCLUSIONS: Men with testicular cancer continue to be at significantly elevated risk of second malignant neoplasms for more than two decades following initial diagnosis. Patterns of excess second cancers suggest that many factors may be involved, although the precise roles of treatment, natural history, diagnostic surveillance, and other influences are yet to be clarified.

Antineoplastic Agents↗
PubMed1997

Are MIBI/tetrofosmin heart studies a potential radiation hazard to technologists?

The number of nuclear medicine studies is increasing and they are becoming more complex and time-consuming. In particular, this is true of myocardial perfusion investigations. We use a one-day protocol for these studies, utilizing 99Tc(m)-MIBI or 99Tc(m)-tetrofosmin with tomographic rest images (250 MBq) acquired in the morning and exercise images (750 MBq) approximately 4 h later after pharmacological stress. Imaging technologists are concerned about continual exposure to 1000 MBq 99Tc(m) per study. Radiation doses were measured during rest (1.0 microSv, n = 18), exercise (2.5 microSv, n = 18) and stress administration (2.0 microSv, n = 16), giving a total dose of 5.5 microSv per combined cardiac study. We have previously shown that the average dose per radionuclide study (excluding myocardial perfusion studies) is 1.5 microSv. Although 5.5 microSv is higher, a technologist is highly unlikely to exceed current dose limits. New EC legislation, however, is expected to reduce these limits, which may lead to more classified workers. Pregnant technologists should avoid, if possible, combined cardiac studies, especially if performing other nuclear medicine duties.

Adenosine↗
PubMed1996

Cervical cancer screening: are the 1989 recommendations still valid? National Workshop on Screening for Cancer of the Cervix.

Although screening for cervical cancer has been shown to be effective in reducing the morbidity and mortality associated with this disease, and despite many attempts to encourage the development of provincial programs, as of 1995 no province had a comprehensive screening program for cervical cancer. Participants at the Interchange '95 workshop, held in Ottawa in November 1995, reviewed the recommendations of the 1989 National Workshop on Screening for Cancer of the Cervix and identified factors that have impeded their implementation. Participants discussed the need for comprehensive information systems, quality control and strategies to increase recruitment of unscreened and underscreened women. They concluded that the formation of a Cervical Cancer Prevention Network involving key stakeholders will facilitate the development and implementation of provincial programs to ensure optimal screening. They agreed that, in the interim, recommendations for practising physicians should remain as they were following the 1989 workshop.

Canada↗
PubMed1996

p53 mutations in lung cancer following radiation therapy for Hodgkin's disease.

High risks of lung cancer occur after successful treatment of Hodgkin's disease. In addition to tobacco smoking, other risk factors include radiotherapy, chemotherapy, and immunosuppression, although the relative contributions of each are unknown. We conducted p53 mutational spectrum analysis in second lung cancers after radiation therapy for Hodgkin's disease in the Netherlands and in Ontario, Canada. Lung cancer tissues from 11 patients were analyzed by p53 immunohistochemistry and DNA sequence analysis. All were male cigarette smokers, all received radiation therapy, and six also received chemotherapy. The lung cancers occurred 9.8 years (mean) after treatment. Radiation doses to lung lobes that developed the tumors averaged 5.7 Gy (range, 3.7-11.7 Gy). Sequence analysis showed four missense and two silent p53 point mutations in five patients. There were four G:C-->A:T transitions; three of four mutated deoxyguanines occurred on the coding strand, and one was a CpG site. There were two transversions: one G:C-->C:G and one A:T-->C:G. Despite moderate or heavy smoking histories in all patients, the mutational spectrum appears to differ from usual smoking-related lung cancers in which G:C-->T:A transversions predominate. The absence of G:C-->T:A mutations and the prominence of G:C-->A:T transitions, which are characteristic of radiation and oxidative damage, suggest that radiotherapy might have caused some of the p53 mutations. These data illustrate the potential of mutation analysis to determine causes of human cancer. If confirmed in a larger series, these results imply that some radiation-induced cancers can be distinguished from those caused by other factors.

Adult↗
PubMed1993

Paternal radiation exposure and leukaemia in offspring: the Ontario case-control study.

OBJECTIVES: To test the hypothesis that there is an association between childhood leukaemia and the occupational exposure of fathers to ionising radiation before a child's conception. DESIGN: Case-control study with eight matched controls per case. SETTING: Regions of Ontario, Canada, with an operating nuclear facility. SUBJECTS: Cases were children (age 0-14) who died from or were diagnosed as having leukaemia from 1950 to 1988 and were born to mothers living in the vicinity of an operating nuclear facility. Controls were identified from birth certificates, matched by date of birth and residence at birth. There were 112 cases and 890 controls. MAIN OUTCOME MEASURES: Paternal radiation exposure was determined by a record linkage to the Canadian National Dose Registry. RESULTS: Six fathers of cases and 53 fathers of controls had had a total whole body dose > 0.0 mSv before the child's conception, resulting in an odds ratio of 0.87 (95% confidence interval 0.32 to 2.34). There was no evidence of an increased leukaemia risk in relation to any exposure period (lifetime or six months or three months before conception) or exposure type (total whole body dose, external whole body dose, or tritium dose), except for radon exposure to uranium miners, which had a large odds ratio that was not significantly different from the null value. CONCLUSIONS: The findings of this study in Ontario did not support the hypothesis that childhood leukaemia is associated with the occupational exposure of fathers to ionising radiation before the child's conception.

Adolescent↗
PubMed1993

Childhood leukemia in the vicinity of Canadian nuclear facilities.

An ecologic study was conducted to determine whether leukemia rates among children born to mothers residing in the vicinity of Ontario (Canada) nuclear facilities differed from the provincial average. Childhood leukemia mortality and incidence ratios for the period 1950 to 1987 were examined for five regions within 25 km of a nuclear facility. The nuclear facilities included a research development facility, a uranium refinery, a uranium mining and milling facility, and two nuclear-power generating stations. Overall, the observed number of leukemia deaths (O = 54) was slightly greater than expected (E = 46.1) during the period when the facilities operated, but the difference was not statistically significant (O/E = 1.17, 95 percent confidence interval [CI] = 0.88-1.53). There was no indication of a birth cohort effect, as the mortality ratios based on place of birth were not significantly greater than the mortality ratios based on place of death. In the analyses of individual facilities, CIs included the null value and were generally wide because of the small observed and expected numbers; however, in the vicinity of the nuclear generating stations, the observed relative excess of leukemia deaths (O = 36, O/E = 1.40) had a lower confidence limit that was close to the null value.

Adolescent↗
PubMed1993

An historical cohort study of cardiac catheterization during childhood and the risk of cancer.

This study aimed to determine whether cancer risk was elevated among patients exposed to radiation from diagnostic cardiac catheterization during childhood. The study cohort included 3915 children who underwent at least one cardiac catheterization at a major children's hospital in Toronto, Canada, between 1950 and 1965, were < or = 18 years at the time of the procedure, and were residents of Ontario. Follow-up of the cohort was done by linkage to the Ontario Cancer Registry up to 1986. A total of seven cancer deaths were observed (O), compared with 5.7 expected (E) based on provincial cancer rates (mortality ratio [O/E] = 1.2; 90% confidence interval [CI] : 0.6-2.3). In the analysis of cancer incidence, 13 cancers were detected, compared with 17.3 expected (O/E = 0.75; 90% CI : 0.4-1.2). These mortality and incidence ratios were not statistically significantly elevated. Detailed analyses were conducted according to age at exposure, age at diagnosis, sex, number of procedures, year of first catheterization, and latent period. Detected deviations in risk were confined to an early period of exposure, indicating that later practices of cardiac catheterization were not associated with increased risk. In general, there was no statistically significant excess risk of cancer among the cohort.

Adolescent↗
PubMed1992

A case-control study of the risk of breast cancer in relation to oral contraceptive use.

The relation of oral contraceptive use to the risk of breast cancer was evaluated in a case-control study of women under the age of 70 years, conducted in Toronto, Canada, from 1982 through 1986. A total of 607 breast cancer cases identified in a cancer hospital were compared with 1,214 controls matched to the cases on neighborhood and decade of age. Information on oral contraceptive use and risk factors for breast cancer was collected in home interviews. Conditional logistic regression was used to control multiple confounding factors. For women aged 40-69 years (527 cases, 1,054 controls), the results suggest that oral contraceptive use does not increase the risk of breast cancer. Multivariate relative risk estimates were close to or below 1.0 for long durations of use overall and in various categories of parity status and other factors. For women under the age of 40 years, the data were sparse (80 cases, 160 controls). Although there were some elevated relative risk estimates, most were not statistically significant, and there were no consistent patterns across duration of use. The present data add to the body of evidence that indicates that oral contraceptive use does not adversely affect the risk of breast cancer in older women; the data are inadequate to clarify the effect in younger women.

Adult↗