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Biomedical subjects

R E Curtis

Publications and source records attributed to R E Curtis.

At least 55 records · Page 3Linked to original sources

Risk of second malignancy after cutaneous T-cell lymphoma.

Risk of second primary malignancy was assessed in a population-based follow-up survey of all persons who developed cutaneous T-cell lymphoma (CTCL) in nine geographic areas of the United States covered by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute during the period 1973 to 1983. Among 544 patients with a first primary tumor reported as CTCL, a second cancer developed in 35 (6%), yielding a significantly elevated relative risk (RR) of 1.7, which reflects excesses for cancers of the lung and colon and non-Hodgkin's lymphoma. Although the excess of lymphoma may be related to the evolution of CTCL to less differentiated T-cell lymphoma, additional studies are needed to clarify the immunologic, genetic, viral, and environmental factors that may contribute to the development of second cancers.

Cohort Studies↗

Leukemia risk following radiotherapy for breast cancer.

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.

Aged↗

Risk of second malignancy after cancers of the renal parenchyma, renal pelvis, and ureter.

Risk of second primary malignancy was assessed in a population-based survey of persons who developed cancers of the renal parenchyma, renal pelvis, or ureter in Connecticut during the period 1935-1982. Among 4176 patients with a first primary tumor of the renal parenchyma, a second cancer was reported in 219 (5%), yielding a small but significantly elevated relative risk (RR) of 1.2, which reflects excesses for cancers of the bladder, kidney, and lymphatic-hematopoietic system. Among 939 patients with a first primary tumor of the renal pelvis or ureter, a second cancer was reported in 155 (17%), associated with a significantly elevated RR of 2.7. This resulted mainly from a 21-fold increase in risk for bladder cancer, although significant excesses were also found for lung and prostate cancers, and metachronous cancers of the renal pelvis and ureter. These associations seem to reflect the multicentric behavior of tumors arising in the urinary tract, the role of cigarette smoking, and host factors yet to be defined, and some degree of heightened medical surveillance and detection of tumors, especially in the same organ system.

Aged↗

Second cancers following radiation treatment for cervical cancer. An international collaboration among cancer registries.

The numbers of second cancers among 182,040 women treated for cervical cancer that were reported to 15 cancer registries in 8 countries were compared to the numbers expected had the same risk prevailed as in the general population. A small 9% excess of second cancers (5,146 observed vs. 4,736 expected) occurred 1 or more years after treatment. Large radiation doses experienced by 82,616 women did not dramatically alter their risk of developing a second cancer; at most, about 162 of 3,324 second cancers (approximately equal to 5%) could be attributed to radiation. The relative risk (RR = 1.1) for developing cancer in organs close to the cervix that had received high radiation exposures--most notably, the bladder, rectum, uterine corpus, ovary, small intestine, bone, and connective tissue--and for developing multiple myeloma increased with time since treatment. No similar increase was seen for 99,424 women not treated with radiation. Only a slight excess of acute and non-lymphocytic leukemia was found among irradiated women (RR = 1.3), and substantially fewer cases were observed than expected on the basis of current radiation risk estimates. The small risk of leukemia may be associated with low doses of radiation absorbed by the bone marrow outside the pelvis, inasmuch as the marrow in the pelvis may have been destroyed or rendered inactive by very large radiotherapy exposures. There was little evidence of a radiation effect for cancers of the stomach, colon, liver, and gallbladder, for melanoma and other skin cancers, or for chronic lymphocytic leukemia despite substantial exposures. An excess of thyroid cancer possibly was related to the low dose received by this organ. Ovarian damage caused by radiation may have been responsible for a low breast cancer risk (RR = 0.7), which was evident even among postmenopausal women. A substantial excess of lung cancer (RR = 3.7) largely may be due to misclassification of metastases and the confounding influence of cigarette smoking. Women who were under 30 or over 50 years of age when irradiated were at greatest absolute risk for developing a second cancer. The RR, however, was higher among those under age 30 years at exposure (RR = 3.9) than among older women. The expression period for radiation-induced solid tumors appeared to continue to the end of life.

Abdominal Neoplasms↗

Second cancer following cancer of the female genital system in Connecticut, 1935-82.

The risk of second primary cancer was evaluated in more than 25,000 women with cancer of the genital organs diagnosed between 1935 and 1982 in Connecticut. Significant excesses of subsequent cancers were observed following cancers of the cervix (35%, n = 656), uterine corpus (16%, n = 1,060), and ovary (58%, n = 366). When observed and expected second cancers of the female genital tract were excluded, these excesses became 40%, 30%, and 59% after cervix, uterine corpus, and ovary, respectively. Among women with either cancer of the cervix or uterine corpus, the risk of developing a second cancer rose with increasing duration of follow-up, reaching an excess of 61 and 34%, respectively, after 20 years. In contrast, among patients with ovarian cancer, the second cancer risk decreased over time to 41% after 10 years. Cancers related to smoking, i.e., oral cavity and pharynx, esophagus, and respiratory system, were notably increased among cervical cancer patients. The twofold to threefold risks observed for these second cancers are consistent with recent evidence linking cervical cancer to cigarette smoking and seem too large to be artifacts of confounding by low socioeconomic status. An increased incidence of second cancer of the abdominal organs (colon, rectum, kidney, bladder, ovaries) was generally observed for each gynecologic site. However, only rectal cancer was consistently linked with radiation treatment for the first primary cancer. Leukemia occurred in excess after cancers of the uterine corpus and ovary, but not after cervical cancer. The predominant cell type was acute nonlymphocytic leukemia, and the excess was associated with radiotherapy for uterine corpus cancer and with chemotherapy for ovarian cancer. Cancers of the breast and colon were increased following uterine corpus and ovarian cancer and vice versa, which supports the notion that these sites share a common etiology, perhaps related to dietary or hormonal factors. Cervical cancer patients experienced a deficit of subsequent breast cancer, possibly due to ovarian removal or ablation by radiation. Investigators need to explore further the association between the smoking-related cancer sites and cervical cancer, to clarify the role of radiotherapy and chemotherapy in relation to excess cancers, and to define more fully the etiologic factors that link cancers of the breast, colon, uterine corpus, and ovary.

Breast Neoplasms↗

Cancer registration in Connecticut and the study of multiple primary cancers, 1935-82.

The Connecticut Tumor Registry (CTR) was established in 1941 and is the oldest population-based cancer registry in the world. Since 1935, all malignant tumors have been registered, and cancer patients are followed annually for vital status. Reporting by hospitals of all cancers diagnosed in Connecticut residents became mandatory in 1971. The reporting physician or hospital makes the initial determination as to whether a tumor is an independent primary cancer, recurrent tumor, or metastatic lesion. In addition, the Registry maintains stringent quality control procedures to avoid duplication of cancer reports. The Registry reviews reports of new cancers developing in patients with a previous primary cancer to rule out the possibility of misdiagnosed metastases. Microscopic confirmation of the diagnosis has improved from 49% in 1935-39 to 94% in 1980-82. Cancers reported only from death certificates currently account for only 1% of all registrations. Between 1935 and 1979, cancer rates in Connecticut almost doubled among males and increased by more than one-third among females; notable increases were seen for cancers of the lung and prostate in males and cancers of the lung and breast in females. In recent years, rates for malignant melanoma of the skin have increased dramatically among both sexes. Stomach cancer has decreased over time in both sexes, as has cervical cancer in females. Although the CTR has used several revisions of the International Classification of Diseases to code the primary site of cancers, rules for the coding of multiple primary cancers have remained essentially the same. Among 253,536 individuals diagnosed between 1935 and 1982 with an invasive cancer, 16,727 (6.6%) nonsimultaneous second cancers were evaluated and are discussed in subsequent chapters of this monograph. Simultaneous cancers were diagnosed in 4,107 individuals and accounted for approximately 20% of all multiple cancers reported in Connecticut. The most frequent simultaneous tumors were cancers of the colon, rectum, prostate, lung, breast, and bladder. Some simultaneous cancers (chronic lymphocytic leukemia, testis, prostate, rectum, uterine corpus, and liver and biliary tract) occurred almost as frequently as the number of subsequent nonsimultaneous tumors, which suggests that the patterns of risk over time for certain sites may be distorted when diagnoses are advanced in time and removed from analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Summary: multiple primary cancers in Connecticut, 1935-82.

The risk of developing a second primary cancer was evaluated in over 250,000 persons reported to the Connecticut Tumor Registry (CTR) during 1935-82. The CTR has collected data on cancer incidence longer than any other population-based tumor registry and thus provided researchers with a unique opportunity to investigate the occurrence of second cancers among persons followed for long periods, in some cases for more than 40 years. When compared with the general Connecticut population, cancer patients had a 31% increased risk of developing a subsequent cancer overall and a 23% elevated risk of second cancer at a different site from the first. Little variation in risk was seen for the first 20 years of follow-up, although the risk for females averaged twice that for males (41% vs. 18%). Persons who survived more than 20 years after the diagnosis of their first cancer were at highest risk: 51% for females and 45% for males. Over 1 million person-years of observation were recorded, and the excess risk of developing a new cancer was 3.5 per 1,000 persons per year. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to developing new cancers in the same or contiguous tissue throughout their lifetimes. A notable finding was the high risk of cancers of the lung, larynx, buccal cavity, and pharynx observed among cervical cancer patients, which suggested a common etiology involving cigarette smoking. The intriguing association previously reported among cancers of the colon, uterine corpus, breast, and ovary was confirmed in our data, which indicated the possible influence of hormonal or dietary factors. Incidental autopsy findings were largely responsible for the observed excesses of second cancers of the prostate and kidney, and heightened medical surveillance of cancer patients likely resulted in ascertainment bias and elevated risks for some tumors during the early period of follow-up, most notably cancers of the thyroid. Interestingly, patients with prostate cancer were the only ones found to be at significantly low risk for second cancer development. However, this might be an artifact of case-finding because advanced age at initial diagnosis of prostate cancer was associated with an underascertainment of second cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Connecticut↗

Introduction to the study of multiple primary cancers.

To lay the groundwork for subsequent chapters in this monograph of multiple primary cancers in Connecticut and Denmark, we present a description of the historical significance of previous studies, focusing on key surveys that have enhanced our understanding of the origins of multiple cancers. Case reports, hospital series, and cancer registry studies have progressively sharpened our perspective on the patterns and causes of multiple cancers. These findings in turn have generated hypotheses about host and environmental determinants of various combinations of cancer and have provided clues to the actual mechanisms of carcinogenesis. The registries of Connecticut and Denmark which began in the 1930s and 1940s, respectively, afford investigators a unique opportunity to analyze the cancer experience of well-defined populations, followed for long periods. The major contribution of this monograph is the evaluation of second cancer risks among long-term survivors of cancer, including relatively rare tumors about which little information currently exists. For patients with a particular cancer, the number of observed second cancers are tabulated over time and compared with those expected if the patients experienced the same rates prevailing in the corresponding general population. We have discussed problems in distinguishing statistical artifacts from biologically plausible associations in light of the potential biases inherent in follow-up surveys of cancer patients; for example, heightened medical surveillance and mistaken metastases could result in false indications of elevated risk. Several differences in the reporting, follow-up, and coding practices between the Connecticut and Denmark registries are described and probably account for many differences in the reported findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Connecticut↗

Risk of leukemia associated with the first course of cancer treatment: an analysis of the Surveillance, Epidemiology, and End Results Program experience.

The risk of leukemia associated with the first course of cancer treatment was evaluated in over 440,000 patients diagnosed during 1973-80 (average follow-up = 1.91 yr) from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Although the reporting of the first course of therapy probably was incomplete, 34 acute nonlymphocytic leukemias (ANLL) developed compared with 7.6 expected among 70,674 patients known to receive initial chemotherapy [relative risk (RR) = 4.5, 95% confidence interval (Cl) = 3.1-6.3]. Significant ANLL excesses were observed following chemotherapy for breast cancer (RR = 8.1), ovarian cancer (RR = 22.2), and multiple myeloma (RR = 9.5). Patients initially treated with radiation (with no record of chemotherapy) also had a significantly increased ANLL risk; 45 leukemias occurred versus 17.9 expected (RR = 2.5, 95% Cl = 1.8-3.4). In this group, excess ANLL were found following irradiation for uterine corpus cancer (RR = 4.0). Kidney and renal pelvis cancer patients had a twofold leukemia risk (all types) that was unrelated to treatment (RR = 2.2).

Antineoplastic Agents↗