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Biomedical subjects

J D Boice

Publications and source records attributed to J D Boice.

At least 181 records · Page 10Linked to original sources
PubMed1988

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Female↗
PubMed1987

Bone sarcomas linked to radiotherapy and chemotherapy in children.

We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (+/- SE) 20-year cumulative risk of 2.8 +/- 0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose-response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose-response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer.

Alkylating Agents↗
PubMed1987

Cancer mortality after multiple fluoroscopic examinations of the chest.

Total cancer deaths were not increased among 2,074 women and 1,277 men who were fluoroscopically examined an average of 73 and 91 times, respectively, during lung-collapse therapy for tuberculosis (TB). Patients who did not receive this form of therapy (2,141 women and 1,418 men) and general population rates were used for comparison. All subjects were discharged alive from eight TB sanatoria in Massachusetts between 1930 and 1954; the average follow-up was 23 years. Deaths due to breast cancer were not increased among exposed females [standardized mortality ratio (SMR) = 1.0, n = 24], and SMRs greater than 2.1 could be excluded with 95% confidence. In contrast to other series, our inability to detect a breast cancer excess was likely due to lower breast doses (66 rad) and higher average ages at exposure (28 yr) and thus lower sensitivity. A deficit of lung cancer among exposed males and females was observed (SMR = 0.8, n = 26), even though increased risks have been observed among other populations exposed to similar dose levels. The estimated average lung dose was 91 rad, and SMRs greater than 1.2 for lung cancer could be excluded with 95% confidence. Overall, this study indicates that the radiation hazard of multiple low-dose exposures experienced over many years is not greater than currently accepted estimates for breast and lung cancer. For lung cancer the radiogenic risk may be less than predicted from high-dose, single-exposure studies.

Adult↗
PubMed1987

Leukemia after therapy with alkylating agents for childhood cancer.

The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.

Alkylating Agents↗
PubMed1987

A population-based case-control study of thyroid cancer.

A population-based case-control interview study of thyroid cancer (159 cases and 285 controls) was conducted in Connecticut. Prior radiotherapy to the head or neck was reported by 12% of the cases and 4% of the controls [odds ratio (OR) = 2.8; 95% confidence interval = 1.2-6.9]. Risk was inversely related to age at irradiation and was highest among children exposed under age 10. Few persons born after 1945 received prior radiotherapy, consistent with the declining use of radiation to treat benign conditions in the 1950's. Among females the radiogenic risk appeared to be potentiated by the number of subsequent live-births. Other significant risk factors included a history of benign thyroid nodules (OR = 33) or goiter (OR = 5.6). Miscarriage and multiparity increased risk but only among women who developed thyroid cancer before age 35 years. Consumption of shellfish (a rich source of iodine) seemed to increase the risk of follicular thyroid cancer, whereas consumption of goitrogen-containing vegetables appeared to reduce risk of total thyroid cancer, possibly because of their cruciferous nature. A significantly low risk was observed among persons of English descent, whereas Italian ancestry appeared to increase risk. No significant associations were found with a number of suspected risk factors: diagnostic x-rays, radioactive isotope scans, occupational radiation exposure, tonsillectomy, Jewish ethnicity, alcohol intake, cigarette smoking, oral contraceptives, lactation suppressants, menopausal estrogens, most other common medications, and water source. New associations were suggested for obesity among females (OR = 1.5), surgically treated benign breast disease (OR = 1.6), use of spironolactone (OR = 4.3) or vitamin D supplements (OR = 1.8), and a family history of thyroid cancer (OR = 5.2). About 9% of the incident thyroid cancers could be attributed to prior head and neck irradiation, 4% to goiter, and 17% to thyroid nodular disease, leaving the etiology of most thyroid cancers yet to be explained.

Adult↗
PubMed1987

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical 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. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Adult↗
PubMed1987

Acute myeloid leukemia and other myelopathic disorders following treatment with alkylating agents.

Several large cohorts of patients treated with alkylating agents served as a means to review the clinical and pathologic features of 55 cases of myelopathic disorders that resulted. The incidence was 1.8% overall and consisted of five patients (9.9%) who developed bone marrow hypoplasia or aplasia, 15 (27.2%) who developed a myelodysplastic syndrome, and 35 cases of acute myeloid leukemia (62.9%). The median time to recognition of MPD was 14 months, following cessation of chemotherapy. The distribution of the treatment-related MDS cases was different than "de novo" MDS with a high percentage of RAEB-T, and with the treatment related AMLs, there were a higher percentage of patients with FAB M6 (erythroleukemia), and no cases of FAB M3 (hypergranular promyelocytic). The median survival of all patients was very brief.

Adolescent↗
PubMed1986

Melphalan may be a more potent leukemogen than cyclophosphamide.

We have evaluated the relation between alkylating agents and leukemic disorders in 3363 1-year survivors of ovarian cancer who were treated in five randomized clinical trials and at two large medical centers. Overall, 28 patients developed acute nonlymphocytic leukemia (expected, 1.2) and 7 developed preleukemia. A 93-fold increased risk for acute nonlymphocytic leukemia was seen in 1794 women treated with chemotherapy; the incidence of leukemic disorders was 7.7/1000 women per year. Risk was highest 5 to 6 years after the first treatment and appeared to decrease thereafter. The use of radiation therapy did not affect risk. The 10-year cumulative risk (mean +/- SE) of acquiring a leukemic disorder was 8.5% +/- 1.6% after treatment with any alkylating agent, 11.2% +/- 2.6% after treatment with melphalan, and 5.4% +/- 3.2% after cyclophosphamide treatment. A dose-response relationship was apparent in 605 women receiving melphalan and suggested in 333 women receiving cyclophosphamide. Women receiving melphalan were two to three times as likely to develop leukemic disorders than were women receiving cyclophosphamide. These data indicate that choice of chemotherapeutic agent and drug dosage may influence significantly the risk for long-term adverse effects of cancer therapy.

Acute Disease↗
PubMed1985

Prenatal x-ray exposure and childhood cancer in twins.

We conducted a case-control study to investigate the relation between prenatal exposure to x-rays and childhood cancer, including leukemia, in over 32,000 twins born in Connecticut from 1930 to 1969. Twins as opposed to single births were chosen for study to reduce the likelihood of medical selection bias, since twins were often exposed to x-rays to diagnose the twin pregnancy or to determine fetal positioning before delivery and not because of medical conditions that may conceivably pre-dispose to cancer. Each of 31 incident cases of cancer, identified by linking the Connecticut twin and tumor registries, was matched with four twin controls according to sex, year of birth, and race. Records of hospitals, radiologists, and private physicians were searched for histories of x-ray exposure and other potentially important risk factors. Documented prenatal x-ray exposures were found for 39 per cent of the cases (12 of 31) and for 26 per cent of the controls (28 of 109). No other pregnancy, delivery, or maternal conditions were associated with cancer risk except low birth weight: 38 per cent of the cases as compared with 25 per cent of the controls weighed under 2.27 kg at birth. When birth weight was adjusted for, twins in whom leukemia or other childhood cancer developed were twice as likely to have been exposed to x-rays in utero as twins who were free of disease (relative risk, 2.4; 95 per cent confidence interval, 1.0 to 5.9). The results, though based on small numbers, provide further evidence that low-dose prenatal irradiation may increase the risk of childhood cancer.

Adolescent↗
PubMed1985

Leukaemia after cervical cancer irradiation in Denmark.

A matched case-control study among cervical cancer patients in Denmark was conducted to evaluate the possible influence of radiation therapy on leukaemia risk. Among 25718 women treated between 1943-1977, 27 cases of leukaemia occurred one or more years after diagnosis. Four controls were matched to each case on age, calendar year of diagnosis and survival without developing a second cancer. Detailed medical records were abstracted, and individual radiation doses to active bone marrow were determined by medical physicists. All leukaemia diagnoses were classified by one haematopathologist. A 2.5-fold risk of radiogenic leukaemia was found, although the excess was not statistically significant (95% Cl = 0.5-12.1). The pattern of risk by dose was somewhat compatible with animal experiments, ie, the risk rose, peaked, and then decreased to near normal levels at the highest dose categories. The average dose to the total bone marrow was 783 rads, and thus a much greater risk of leukaemia was predicted on the basis of estimates from other exposed populations. Assuming that the pelvic bone marrow is essentially destroyed by high-dose radiotherapy and should, perhaps, be disregarded for the purpose of risk estimation, risk coefficients consistent with other studies can be computed. Nonetheless, the very low risk of radiogenic leukaemia found among cervical cancer patients suggests that the induction of leukaemia by radiation is a complex function of dose, and that very high doses may result in a decreased risk, possibly associated with cellular sterilization or other mechanisms.

Acute Disease↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Second cancer following cutaneous melanoma and cancers of the brain, thyroid, connective tissue, bone, and eye in Connecticut, 1935-82.

The risk of second primary cancers developing was evaluated in individuals with 6 rare tumors in Connecticut between 1935 and 1982. Small but significant excesses of all second cancers occurred in patients with cutaneous melanoma (42%), and cancers of the brain (59%), thyroid (49%), connective tissue (23%), bone (66%), and eye (40%). In individuals with cutaneous melanoma, the highest risks were for subsequent cutaneous melanomas [relative risk (RR) = 8.5] that persisted throughout all intervals of observation. The risk for second melanomas was higher in persons under age 40, consistent with a heritable component. Connective tissue tumors and breast cancers also occurred in excess. Among patients with brain cancer, an increase of melanoma was observed that may represent an underlying neural crest abnormality, although no excess of brain cancer was seen after melanoma. Reciprocal increases of bone cancer after connective tissue cancer and connective tissue cancer after bone cancer point to shared risk factors, such as high dose radiotherapy or genetic susceptibility states. An anticipated high risk of osteogenic sarcoma following Ewing's sarcoma was not seen. An excess of breast cancer (RR = 1.9) after thyroid cancer indicates common etiologic factors. Expected excesses of bilateral retinoblastoma and bone cancer after retinoblastoma were seen. Tumors commonly treated with alkylating agents or nitrosoureas (melanoma, brain, connective tissue) showed slightly elevated risks of acute nonlymphocytic leukemia. Prostate cancer was frequently found to be in excess, but this is likely an artifact due to ascertainment bias.

Bone Neoplasms↗
PubMed1985

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↗
PubMed1985

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↗