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Biomedical subjects

J D Boice

Publications and source records attributed to J D Boice.

At least 199 records · Page 11Linked to original sources
PubMed1985

Second cancer following cancer of the respiratory system in Connecticut, 1935-1982.

The risk of a person developing a second primary cancer was evaluated in approximately 30,000 persons who developed cancer of the respiratory system in Connecticut between 1935 and 1982. A significant 44% excess of all second cancers was observed following cancer of the lung (614 observed vs. 426 expected). The excess of second tumors was 72% following cancer of the larynx (541 vs. 314) and 34% following cancer of the nasal cavities and sinuses (43 vs. 32). For cancers of the lung and larynx, second cancers arose mainly along the respiratory tract or other sites associated with cigarette smoking (oral cavity, bladder, kidney). A threefold excess of esophageal cancer followed cancer of the larynx, which was indicative of risk factors in common (alcohol and tobacco) and possibly an effect of radiotherapy. Radiotherapy may have contributed also to the increased risk of second lung and breast cancers. A slight excess risk of leukemia after lung cancer points to a possible effect of chemotherapy given for certain histologic types. An unexpected finding was a significant 50% increased risk of colon cancer following cancer of the larynx. Significant excesses of prostate cancer are probably artifacts associated with increased medical surveillance and higher autopsy rates among cancer patients than in the general population. No deficits of any second cancers were observed. The risk of a second cancer developing did not appear to vary by sex or time since initial diagnosis, except that the risks following cancer of the nasal cavities and sinuses returned to normal levels among long-term survivors. Among persons observed for 10 or more years after their initial diagnosis of cancers of the lung or larynx, the risk of developing a second cancer remained high, i.e., on the order of 50% above expectation. Further analytic studies should clarify the role of smoking, alcohol, other life-style and host factors, and various forms of therapy on the risk of second cancers following cancer of the respiratory system.

Connecticut↗
PubMed1984

Endometrial cancer following treatment for breast cancer: a case-control study in Denmark.

To evaluate the risk of endometrial cancer subsequent to breast cancer, a case-control study was carried out in Denmark. Between 1943-1977, 115 cases of histologically confirmed endometrial carcinoma developed more than 3 months after the diagnosis of a primary breast cancer in 51,638 women. A total of 235 breast cancer patients with no second primary cancer were matched to the cases on age, calendar year of diagnosis, and survival with an intact uterus. Identification of cases and controls relied upon records available in the Danish Cancer Registry. Information on risk factors and reproductive histories was abstracted from hospital records. Increased relative risks (RR) for endometrial cancer were associated with menopausal oestrogen use (RR = 4.9), nulliparity (RR = 2.1), late age at natural menopause (RR = 2.9), and pelvic irradiation (RR = 1.4). No association was apparent for drugs used to treat breast cancer. This study indicates that breast and endometrial cancer share several common aetiologic factors and that studies of second primary cancers have the potential to provide information on risk factors other than those associated with therapy.

Age Factors↗
PubMed1983

Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU).

We evaluated the risk of acute nonlymphocytic leukemia, acute myelodysplastic syndrome, and preleukemia in 3633 patients with gastrointestinal cancer who were treated in nine randomized clinical trials. Among 2067 patients given semustine (methyl-CCNU) as adjuvant therapy, leukemic disorders developed in 14, whereas only one leukemic disorder (acute nonlymphocytic leukemia) occurred among 1566 patients given other therapies (relative risk = 12.4; 95 per cent confidence interval = 1.7 to 250). The six-year cumulative mean risk (+/- S.E.) of acquiring a leukemic disorder after treatment with semustine was 4.0 +/- 2.2 per cent; the incidence rate was 2.3 cases per 1000 persons per year. Risk increased significantly with time after treatment. The risk of leukemic disorders did not differ according to sex, race, age at treatment, or initial tumor type, nor was it enhanced by concomitant radiotherapy or immunotherapy. In addition, no excess of acute nonlymphocytic leukemia was seen in 44,370 patients treated for gastrointestinal cancer in Connecticut during the period 1935 to 1974, before the advent of nitrosourea chemotherapy. This study provides quantitative evidence that nitrosoureas are leukemogenic in human beings and confirms previous observations that adjuvant chemotherapy with alkylating agents may increase the risk of leukemia.

Acute Disease↗
PubMed1983

A retrospective cohort analysis of second breast cancer risk for primary breast cancer patients with an assessment of the effect of radiation therapy.

Second breast cancer experience was examined for 27,175 primary breast cancer patients diagnosed in the State of Connecticut during 1935-75 with follow-up for second breast cancers through 1980. The overall ratio of observed to expected second breast cancers was 3.2. Relative risk was found to be inversely related to age at diagnosis and directly related to stage of the first breast cancer. The overall risk of second breast cancers was 711 per 100,000 person-years at risk. Risk of second breast cancers showed a similar relationship to age and stage as relative risk and was also directly related to calendar period of diagnosis of the first breast cancer. Some interactions were observed because patients less than 45 years old at diagnosis with positive nodes had elevated risks and relative risks in the early followup period, whereas less of an effect of stage on relative risk and risk was seen for older patients. The effect of the use of adjunctive radiation therapy on second breast cancer risk was also assessed by the ratio of the risk of second breast cancers for those patients who received both surgery and radiation to the risk of those patients who only received surgery being estimated for patients diagnosed during 1935-59 and for patients diagnosed during 1960-75. For both cohorts relative risks of 1.2-1.4 were found for the 5-year period immediately following diagnosis, likely resulting from the uncontrolled effect of stage in the analysis. Elevated long-term relative risks were not found for patients diagnosed during 1935-59. A long-term marginally statistically significant relative risk of 1.4 (greater than or equal to 10 yr after diagnosis) was found for patients diagnosed during 1960-75. The data do not indicate an overall pattern of relative risks consistent with an effect on long-term second breast cancer risk of radiation exposure to the opposite breast incurred during adjunctive radiation therapy for a first breast cancer.

Age Factors↗
PubMed1982

Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer: a study of five randomized clinical trials.

We evaluated the occurrence of acute nonlymphocytic leukemia (ANL) among 1399 women with ovarian cancer who were treated in five randomized clinical trials. Of the 1399 women, 998 had been treated with alkylating agents, and among these, 12 cases of ANL were observed; the expected number was 0.11. Ten patients with ANL had received melphalan, and two chlorambucil. ANL was not observed in 401 women who had been treated with surgery or radiation or both, without alkylating agents. The excess risk of ANL that was associated with alkylating-agent therapy was 5.8 cases per 1000 women per year, and the cumulative seven-year risk of ANL among patients who were treated with chemotherapy alone was indistinguishable from that observed in patients receiving both radiation and chemotherapy. A positive correlation between initial drug dose and the risk of ANL was suggested. These data underscore the need to assess other cytotoxic agents and regimens of drug administration to identify those that do not have harmful late effects.

Acute Disease↗
PubMed1982

Second cancers following radiotherapy for cervical cancer.

Incidence of second primary cancers was evaluated in 7,127 women with invasive cancer of the cervix uteri, diagnosed between 1935 and 1978, and followed up to 38 years (average, 8.9 yr) in Connecticut. Among 5,997 women treated with radiation, 449 developed second primary cancers compared with 313 expected (relative risk = 1.4) on the basis of rates from the Connecticut Tumor Registry. Excess incidence was noticeable 15 years or more after radiotherapy and attributed mostly to cancers of sites in or near the radiation field, especially the bladder, kidneys, rectum, corpus uteri, and ovaries. No excess was found for these sites among the 1,130 nonirradiated women. The ratio of observed to expected cancers for these sites did not vary appreciably by age at irradiation. The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer.

Adult↗
PubMed1981

Cancer following medical irradiation.

Several generalizations about radiation carcinogenesis can be made: 1) a single exposure is sufficient to elevate cancer incidence many years later: 2) radiation-induced cancer cannot be distinguished from naturally occurring cancer, i.e., there is not unique radiogenic cancer; 3) all cancers appear to be increased after irradiation with the exception of chronic lymphocytic leukemia, and possibly Hodgkin's disease, cervical cancer, and a few others; 4) the breast, thyroid, and bone marrow appear especially radiosensitive; 5) leukemia is the most prominent radiogenic tumor and shows a wave-like pattern of excess incidence over time, and the excess begins within two to four years, peaks about six to eight years, and decreases to normal levels about 25 years later; 6) solid tumors have a minimum latent period of about ten years, and for several cancers, the temporal pattern of incidence appears to follow the natural incidence, i.e., the cancers do not occur before the ages normally associated with increased incidence, implying that age-dependent factors influence the expression of disease; 7) age at exposure is perhaps the most important host factor influencing subsequent cancer risk; 8) the percentage increase in cancer incidence per rad is not the same for all cancers, i.e., some cancer of high natural incidence, e.g., colon, have low "relative risks" and some cancers of low natural incidence, e.g., thyroid, have high "relative risks;" 9) dose-effect curves are often linear, but curvilinearity is also observed and is possibly associated with the need for "two ionizing events" for transformation to occur at low doses, the influence of cell sterilization at moderate doses, the likelihood of "wasted" dose at high doses, and/or the influence of factors that effect the expression of disease.

Adolescent↗
PubMed1981

Cancer mortality in women after repeated fluoroscopic examinations of the chest.

Among 1,047 women fluoroscopically examined in average of 102 times during pneumothorax therapy for tuberculosis and followed up to 45 years (average = 27 yr), no increase in the total number of cancer deaths occurred when these women were compared to 717 women who received other treatments [relative risk (RR) = 0.8]. However, elevated risks of mortality from stomach cancer (RR = 2.3), rectal cancer (RR = 3.8), breast cancer (RR = 1.2), lung cancer (RR = 1.8), and leukemia (RR = 1.2) were observed, but none was statistically significant and all were based on very small numbers of deaths. These increases were balanced by decreases of genital cancer (RR = 0.2), pancreatic cancer (RR = 0.9), lymphoma (RR = 0.6), and all other cancers (RR = 0.1). Average cumulative absorbed doses were 110 rads for the lungs, 33 rads for the trunk, 13 rads for the active bone marrow, and 7 rads for the stomach. The following upper levels of excess risk could be excluded with 95% confidence: 3.5 deaths/10(6) woman-year (WY)-rad for lung cancer, 4.8 deaths/10(6) WY-rad for lymphoma, and 12 deaths/10(6) WY-rad for leukemia. These findings indicated that the carcinogenic effect of multiple low-dose X-ray exposures was not greater than that currently assumed.

Adolescent↗
PubMed1980

Late effects following isoniazid therapy.

Amont 338 women treated in Massachusetts with isoniazid (isonicotinic acid hydrazide = INH) for pulmonary tuberculosis, no excess cancer deaths occurred (8 observed vs 8.3 expected) after 23 years (12.9 mean) of follow-up. There was an excess of cancer deaths (54 vs 35.7) among 1,090 patients who did not receive INH, partly due to radiogenic breast cancer resulting from multiple chest fluoroscopies to monitor pneumothorax. Increased deaths from liver cirrhosis (5 vs 0.8) were observed following INH use, suggesting that chronic as well as acute liver disease complicate this treatment.

Adolescent↗
PubMed1980

Late effects of low-dose adjuvant chemotherapy in colorectal cancer.

As part of a systematic program to evaluate the late effects of antineoplastic therapy in randomized clinical trials, patients enrolled in the low-dose thio-TEPA (TSPA) and 5-fluoro-2'-deoxyuridine (FdUrd) adjuvant colorectal cancer protocols of the Veterans Administration (VA) Surgical Oncology Group between 1958 and 1964 were studied. All patients received surgery with curative intent; 470 also received TSPA, 176 received FdUrd, and 867 received surgery only. The unique VA system permitted complete follow-up through 1977, with 10,902 person-years of observation accrued among 1,613 male patients (mean survival = 6.8 yr). Expected mortality and cancer incidence were computed by applying U.S. Mortality Statistics and Connecticut Tumor Registry age-, race-, sex-, and calendar time-specific rates to the person-years of observation. The mortality experience of the 3 groups was similar. Overall, there was a significant excess in total mortality (observed/expected = 1,359/553) attributable mainly to colorectal cancer (584/14), arteriosclerotic heart disease (258/215.9), pneumonia (41/17), gastric and duodenal ulcers (15/4), and cirrhosis (14/6). No excess mortality from noncolorectal cancers was apparent, nor were there significant differences by treatment: TSPA (22/22), FdUrd (9/12), and surgery only (50/42). Among 1,402 white patients, no significant excess of incident noncolorectal cancers were observed among patients treated with TSPA (30/31, FdUrd (14/15), or surgery only (63/58). Seven incident cases of leukemia developed (4.1 expected) among all patients of various groups: TSPA (3/1.3), FdUrd (1/0.6), and surgery only (3/2.2). No excess of new primary cancers was observed among 211 nonwhite patients. An inverse relationship between the occurrence of second primary cancer and age at diagnosis, irrespective of therapy, was suggested. The results demonstrated the feasibility of this approach for assessment of late complications of anticancer therapy and suggested no measurable carcinogenic effect following very low doses of TSPA and FdUrd in a population of this size.

Adult↗
PubMed1980

Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women.

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three population, at least for age 10-40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.

Adolescent↗
PubMed1980

Leukemia in women following radiotherapy for cervical cancer: ten-year follow-up of an international study.

An international collaborative study of 31,219 women treated for cervical cancer from 30 radiotherapy centers in nine countries was conducted. Patients were followed clinically and with blood studies between 1960 and 1970, and 148,000 woman-years (WY) were accumulated. Among 28,490 women treated with either intercavitary radium, external radiation, or both, 134,000 WY were accumulated and 13 cases of leukemia were observed. On the basis of general population rates, 15.5 cases were expected [relative risk (RR) = 0.8; 95% confidence limits (CL) = 0.4-1.4]. A twofold risk could thus be excluded, but a 1.4-fold risk remained possible. In absolute terms, risks larger than 0.1 leukemia cases per 10(6) WY-rad could be excluded. Among 2,729 cervical cancer patients not irradiated but similarly evaluated, 14,000 WY were accumulated and 2 cases of leukemia were observed as compared with 1.0 expected. In the interval 4-8 years after exposure, the period in which any leukemogenic effect might be most apparent, 7 cases of leukemia were observed among exposed patients as compared with 5.4 expected (RR - 1.3; 95% CL = 0.5-2.7). The absence of an increased leukemia risk suggested that the radiation regimens used to treat cervical cancer are not so effective in inducing leukemia as are other radiation exposures that have been studied.

Age Factors↗
PubMed1980

Techniques for detecting and determining risks from low-level radiation.

Epidemiology is the study of disease in man. In evaluating radiation hazards, analytic studies have utilized the cohort type of investigation (where persons exposed and not exposed to radiation are followed forward in time for determination of disease experience) or case-control approaches (where persons with and without a specific disease are evaluated for previous exposure to radiation). Most radiation studies have evaluated cohorts (e.g., radiologists), although important case-control studies have been conducted (e.g., childhood leukemia as related to prenatal x ray). At its best, epidemiology is capable fo evaluating relative risks (RR) on the order of 1.4 (i.e., a 40% relative excess). However, the RRs of interest following low doses of radiation (1 rad) are on the order of 1.02-1.002. Thus, not much should be anticipated from direct observations at 1 rad, and indirect approaches must be taken to estimate low-dose effects. Such indirect approaches include evaluating 1) populations exposed to a range of doses, both low and high, where interpolation models can be reasonably applied to estimate low-dose effects; and 2) populations exposed to fractionated doses over a long period of time where the resulting dose-effect relationship theoretically should be linear and the estimation of low-level health effects facilitated.

Epidemiologic Methods↗
PubMed1979

Risk of breast cancer following low-dose radiation exposure.

Risk of breast cancer following radiation exposure was studied, based on surveys of tuberculosis patients who had multiple fluoroscopic examinations of the chest, mastitis patients given radiotherapy, and atomic bomb survivors. Analysis suggests that the risk is greatest for persons exposed as adolescents, although exposure at all ages carries some risk. The dose-response relationship was consistent with linearity in all studies. Direct evidence of radiation risk at doses under 0.5 Gy (50 rad) is apparent among A-bomb survivors. Fractionation does not appear to diminish risk, nor does time since exposure (even after 45 years of observation). The interval between exposure and the clinical appearance of radiogenic breast cancer may be mediated by hormonal or other age-related factors but is unrelated to dose. Age-specific absolute risk estimates for all studies are remarkably similar. The best estimate of risk among American women exposed after age 20 is 6.6 excess cancers/10(4) WY-G-Y (10(6) WY-rad).

Adolescent↗
PubMed1978

Follow-up methods to trace women treated for pulmonary tuberculosis, 1930-1954.

A retrospective cohort study, designed to examine the relationship between multiple chest fluoroscopies and subsequent breast cancer risk, was conducted in which 93.6% of 1764 former sanatorium patients were successfully located. The methodology used to trace former female patients who were treated for pulmonary tuberculosis between 1930 and 1954 (20-45 years before the study began) is presented. Extensive use of city directories and telephone resulted in locating the majority of study subjects. Outpatient medical records and state vital statistics departments were also of value. Searching for death certificates of parents was helpful as the informant named on the certificate was often the woman being traced or her husband. The Postal Service was of limited use. No difference in the proportion of breast cancer cases was found between the more easily traced patients and the last 9.7% of patients who were difficult to locate. Fewer of the last patients located had died, however, than those located without intense effort. Patients lost to follow-up were younger at the time of sanatorium admission, had a higher proportion of Protestants and non-white women, had shorter lengths of hospitalization and had less severe tuberculosis requiring less aggressive treatment than patients located.

Adolescent↗