Lung cancer risk and radiation dose among women treated for breast cancer.

BACKGROUND: Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose. PURPOSE: This study evaluated the long-term risk of lung cancer among women treated with radiation for breast cancer. METHODS: In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. RESULTS: For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. CONCLUSIONS: Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high-dose cell killing or the fractionated nature of the exposure. IMPLICATIONS: Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10,000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects.

Uterine cervical carcinoma in Connecticut, 1935-1973: evidence for two classes of invasive disease.

The Connecticut Tumor Registry recorded 5,781 women with carcinoma in situ (CIS) and 7,614 with invasive cervical cancer from 1935 to 1973. True incidence rates for invasive disease were calculated. CIS rates indicated newly diagnosed cases, but true CIS incidence is unknown. Starting in 1945-49, the incidence of invasive cervical declined about 20% in Connecticut before CIS screening could have influenced the disease to that extent. Continuing declines in invasive disease rates after 1955 in Connecticut were probably attributable largely to screening. The persistent occurrence of invasive disease in screened populations and the rapid progression of cancer, with early death among some women with apparently localized disease at diagnosis, suggested that a second class of invasive cervical cancer may exist. Cancers in this class may develop and progress rapidly without a practical possibility of detection in the premalignant stage by cytologic methods. Other screening methods, e.g., metabolic, hormonal, immunologic, or virologic, may be required to control this disease.

Cancer incidence among cosmetologists.

This cohort study examined cancer incidence in 13,650 Connecticut cosmetologists who had held licenses for 5 years or more and had begun hairdressing school prior to January 1, 1966. Cancer incidence rates for the general Connecticut population, 1935-78, were compared with those for 11,845 female and 1,805 male cosmetologists. The females had a standardized cancer incidence ratio (SIR) of 112 (P less than .01). A significant excess of lung cancer (SIR = 141) and excesses of brain (SIR = 168) and ovarian cancer (SIR = 134) of borderline significance were observed. No significant cancer risk was evident for female cosmetologists licensed since 1935, even for those with 35 years or more of follow-up, although the SIRs for brain cancer, lymphoma, and leukemia were elevated. Female cosmetologists who entered the profession between 1925 and 1934, however, experienced a significant overall cancer incidence (SIR = 129) and significant excesses of respiratory, breast, corpus uterine, and ovarian cancers. Those with 35 years or more from time of first license appeared to be at the highest risk. Among males the overall cancer incidence rate was close to that expected (SIR = 105). Smoking habits and reproductive factors that could not be taken into account may explain some of the excesses among females. Although no specific occupational agent could be identified, the excess numbers of leukemias in females and brain cancers among males and females merit continued surveillance.

Cancer in mothers of dizygotic twins.

For the determination of whether mothers of dizygous (DZ) male-female twins or other polyzygous (unlike sexed) multiple births have cancer incidence different from that of controls, a cohort study was conducted with the use of the records of the Connecticut Twin Registry and the Connecticut Tumor Registry (CTR). A total of 3,982 women born between 1885 and 1935 who had borne DZ (male-female) twins or who had experienced other polyzygous multiple births in Connecticut during 1925-59 and a control group of 3,982 women, matched pairwise on year of childbirth, age, number of previous children, race, and national origin, were searched in the CTR for the incidence of cancer of all sites. Women who have DZ twins have a higher level of gonadotropins than women in the general population. A hypothesis that mothers of DZ twins may have a higher incidence of breast cancers than other women was investigated; the results did not support the hypothesis. There was, however, an excess incidence of cancer of the pancreas among mothers of twins. The relative risk was 3.2 (P = 0.026, exact two-tail probability) with exact 95% confidence limits (1.12, 11.16). These results are consistent with findings from autopsy data which suggested that among women but not among men with pancreatic duct cell carcinoma, there is excessive gonadotropic activity. These results are also consistent with early findings of high follicle-stimulating hormone (FSH) in the urine of diabetics and high FSH in the urine of postmenopausal women.

Bladder tumor incidence among workers exposed to benzidine: a thirty-year follow-up.

Linkage with records of the Connecticut Tumor Registry was used to determine cancer incidence in a cohort of workers (n = 984) at a benzidine manufacturing facility. Compared to the findings for the Connecticut population, there was a statistically significant excess of bladder tumor among male cohort members [standardized incidence ratio (SIR) = 343; 95% confidence limits (CL) = 148, 676; n = 830], which was confined to those with the highest estimated level of benzidine exposure (SIR = 1,303; CL = 479, 2,839; n = 105). No significantly elevated risks were found for cancers at other anatomic sites in men or at any anatomic sites in women; nor was there any pattern of increasing risk with increasing benzidine exposure for sites other than bladder. In addition, the elevated bladder cancer risk was greater for men first employed during the earliest years of the plant, namely, 1945-49 (SIR = 976; CL = 262, 2,498) as compared to those first employed in 1950-54 (SIR = 213; CL = 3, 1,184) after equalization of duration of follow-up. These results suggest that the major preventive measures instituted around 1950 may have reduced bladder cancer risk in this plant.

Epidemiology of renal cell carcinoma in Connecticut, 1935-1973.

Data on over 3,700 patients with renal cell carcinoma, reported to the Connecticut Tumor Registry from 1935 through 1973, were used to assess incidence, survival, and associations of risk with demographic characteristics. Incidence increased over time among men, but not among women; a birth cohort effect suggesting increasing incidence rate over time was demonstrated for men. A comparison of male and female age-specific incidence rates indicated that, in the 15- to 39-year-old age group, men were three times more likely than women to develop the disease; after age 40, renal cell carcinoma was diagnosed in men twice as often as in women. Survival probability has increased from 1940 to the present time. A high density of persons per square mile was associated with a higher-than-expected incidence. No trends in incidence according to socioeconomic status were observed.

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.

Nasopharyngeal cancer, sinonasal cancer, and occupations related to formaldehyde: a case-control study.

Formaldehyde vapor induces cancer of the nasal passages in laboratory animals. In this case-control epidemiologic study, occupational information was obtained for 198 persons with sinonasal cancer (SNC), for 173 with nasopharyngeal cancer (NPC) identified as incident cases by the Connecticut Tumor Registry over 41 years among Connecticut males dying of any cause, and for 605 controls sampled from Connecticut death certificates. City directories and death certificates provided information on job, industry, employer, and year of employment for exposure classification. Without knowledge as to case-control status, an industrial hygienist particularly experienced in epidemiologic studies of formaldehyde classified each study subject with respect to probability and degree of formaldehyde exposure. For those with probable exposure to the high level 20+ years prior to death the odds ratio for NPC was 2.3 [95% confidence limits (CL): 0.9, 6.0], and for those with this same risk factor among men dying at age 68+ (the median study age at death or older) the odds ratio was 4.0 [95% CL: 1.3, 12.0--with two-sided P = .015, unadjusted for multiple significance tests, and with two-sided P = .129 in testing for interaction between this risk factor (never any exposure vs. probable exposure to high level 20+ years prior to death) and age (age less than 68 yr vs. age 68+ yr)]. Odds ratios were close to unity for 9 of 13 industries. Formaldehyde-related occupations in printing appeared to be associated with any type of nasal cancer (either SNC or NPC).

Cancer risk among women exposed to exogenous estrogens during pregnancy.

A cohort of 3,139 obstetric patients, who delivered children between 1946 and 1965, was followed retrospectively to assess the relationship between exposure to diethylstilbestrol [(DES) CAS: 56-53-1; alpha, alpha'-diethyl-4,4'-stilbenediol] or other estrogenic substances during pregnancy and subsequent cancer incidence. Among the 1,531 women exposed to DES, the relative risk (RR) for all cancers was 1.46 [95% confidence interval (CI), 1.07-2.00]. The RR for cancers of the breast, cervix, and ovary were 1.37 (adjusted), 1.40, and 2.83, respectively, but none of these estimates was statistically significant. For breast cancer an RR in excess of 2.28 can be excluded, with 95% CI for doses averaging 2,100 mg. Within the exposed group there was no evidence for a dose-response relationship.

Time period compared to birth cohort in Connecticut incidence rates for twenty-five malignant neoplasms.

Out of necessity and convenience many reports on population-based rates for cancer are limited to analyses by time period of diagnosis, and just how often cohort effects are important in cancer data has not been fully explored. To address this question, Connecticut cancer incidence rates for the years 1940-79 were fitted to the model: Log (incidence rate) = constant + age effect + period effect + birth cohort effect + error term. Data for each cancer site and sex were categorized into 10-year intervals by time period and age group. Significance testing for the curvilinear effects (which are estimable functions) of age (A), period (P), and cohort (C) in the 44 data sets led to no clear choice of model for three data sets; an APC model for 20, an AP model for 7, and an AC model for 14. These choices were corroborated by the RA2 index. Limitations in the interpretation of the results were enumerated. Presentation of population-based cancer rates by implicitly assuming an AP model is valuable (e.g., for studying age distribution in different regions or for age-adjustment in examining international variation or time trends). However, the assumption of an AP model may often be incorrect, as was shown to be the case for most of these 44 data sets. The implications for monitoring trends and generating etiologic hypotheses were discussed in light of the results for cutaneous malignant melanoma and cancers of the cervix, breast, ovary, lung, and bladder.

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.

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.

Cigarette smoking and changes in the histopathology of lung cancer.

BACKGROUND: Adenocarcinoma of the lung, once considered minimally related to cigarette smoking, has become the most common type of lung cancer in the United States. The increased incidence of this cancer might be explained by advances in diagnostic technology (i.e., increased ability to perform biopsies on tumors in smaller, more distal airways), changes in cigarette design (e.g., the adoption of filtertips), or changes in smoking practices. We examined data from the Connecticut Tumor Registry and two American Cancer Society studies to explore these possibilities. METHODS: Connecticut Tumor Registry data from 1959 through 1991 were analyzed to determine whether the increase in lung adenocarcinoma observed during that period could be best described by birth cohort effects (i.e., generational changes in cigarette smoking) or calendar period effects (i.e., diagnostic advances). Associations between cigarette smoking and death from specific types of lung cancer during the first 2 years of follow-up in Cancer Prevention Study I (CPS-I), initiated in 1959) and Cancer Prevention Study II (CPS-II, initiated in 1982) were also examined. RESULTS: Adenocarcinoma incidence in Connecticut increased nearly 17-fold in women and nearly 10-fold in men from 1959 through 1991. The increases followed a clear birth cohort pattern, paralleling gender and generational changes in smoking more than diagnostic advances. Cigarette smoking became more strongly associated with death from lung adenocarcinoma in CPS-II compared with CPS-I, with relative risks of 19.0 (95% confidence interval [CI] = 8.3-47.7) for men and 8.1 (95% CI = 4.5-14.6) for women in CPS-II and 4.6 (95% CI = 1.7-12.6) for men and 1.5 (0.3-7.7) for women in CPS-I. CONCLUSIONS: The increase in lung adenocarcinoma since the 1950s is more consistent with changes in smoking behavior and cigarette design than with diagnostic advances.

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.

Leukemia following chemotherapy for breast cancer.

Leukemia following chemotherapy for breast cancer was studied among patients diagnosed during 1973-1985 within the population-based tumor registries in the Surveillance, Epidemiology, and End Results Program. Among 13,734 women given initial chemotherapy, 24 developed acute nonlymphocytic leukemia (ANLL) compared to 2.1 expected based on general population rates (observed/expected = 11.5; 95% confidence interval = 7.4-17.1). Overall, 58 excess ANLL occurred per 100,000 women-years at risk for patients treated with chemotherapy. The cumulative incidence was 0.7% at 10 years. Risk remained high over all periods of observation up to 9 years after treatment. Among 7974 women treated only with surgery during 1973 and 1974, a period before the widespread use of adjuvant chemotherapy for breast cancer, ANLL was not significantly increased (observed = 7, expected = 5.1). A case-control study was then conducted in Connecticut to evaluate in more detail the risk associated with adjuvant chemotherapy in the general population. Among 20 cases (17 incident leukemias and 3 deaths due to preleukemia) and 60 matched controls, alkylating agents were linked to an 11.9-fold risk of ANLL and preleukemia (95% confidence interval = 2.6-55). Chemotherapy regimens including melphalan were related to a higher risk of leukemic conditions than those including cyclophosphamide. These data suggest that women in the general population treated with adjuvant chemotherapy for breast cancer are at an increased risk of leukemia, that the risk remains high among long-term survivors, and that risk differs by type of alkylating agent administered.

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.

Intracranial neoplasms in infants.

Fifty-four primary intracranial neoplasms occurred in infants (18 months of age or younger) in Connecticut during a 40-year period, 1935 to 1974. Thirty percent were medulloblastomas and 16% were ependymal neoplasms. An equal number of males and females were affected. Forty percent were located in the cerebellum, 37% in the cerebral hemispheres, and 17% in the brain stem. The most common symptom was vomiting. Abnormally large head circumference was the most common physical finding. Average survival was 43 months. Survival relative to histopathologic type and location of the neoplasm is discussed. Eighteen patients survived longer than one year and the level of neurological function of these longer survivors is presented.

Clear cell adenocarcinoma of the vagina and cervix: incidence, undetected disease, and diethylstilbestrol.

We conducted an incidence study to determine the occurrence rates of clear cell adenocarcinoma (CCAC) of the vagina and cervix in young women (born in 1940 and thereafter), and a case-series analysis, focusing on the maternal history of pregnancy and delivery and in-utero exposure to diethylstilbestrol (DES). Overall, 10 cases of CCAC had been listed in the files of the Connecticut State Tumor Registry prior to the study, and each of the 10 cases were confirmed as valid. In addition, another 10 cases, all previously undetected, were found after the tissue slides of young women listed as having other cancers of the vagina and cervix were reviewed by expert pathologists, suggesting that prior estimates of the incidence rate for CCAC must be misleading unless special efforts are taken to identify undetected cases. The incidence rates of vaginal CCAC (11 cases total) were highest in 1975-1979, and decreased slightly during 1980-1982. In the cervix (nine cases total), the rate increased consistently since 1970. History of in-utero exposure to diethylstilbestrol was obtained for five of eight vaginal cases and four of eight cervical cases of CCAC. In all nine cases, exposure to diethylstilbestrol was associated with a history of bleeding during the pregnancy or prior miscarriage. We conclude that the finding of stable (or rising) incidence rates for CCAC occurring nearly 30 years after the marked decrease in diethylstilbestrol sales emphasizes the need for continued clinical and epidemiologic studies of the etiology and clinical course of CCAC.

Testicular cancer in the United States: trends in incidence and mortality.

The patterns of incidence and mortality of testicular cancer in the United States indicate substantial differences by age, race, time period, and geographical region. An epidemic increase over time in the risk of testicular cancer is noted for young men aged 15-44, with the most recent birth cohorts showing the greatest rate of increase. Indeed, some of the evidence suggests the possibility of two separate increases, one apparent from at least the late 1930's through the late 1950's and the second appearing in the late 1970's. The incidence data for blacks also show a young adult peak, even though the rates for whites are four to five times higher than for blacks at all ages except early childhood. Mortality rates for older men consistently declined over the 30-year period, while rates for younger men showed a dramatic drop only for the most recent time period. Aetiological factors yet to be determined may be responsible for the increasing incidence of testicular cancer in young adults. Survival factors appear to explain the age-specific differences between the incidence and mortality curves over time.

Malignant melanoma of the vagina--report of 19 cases.

Sixteen previously unreported cases of primary vaginal melanoma were studied, 8 from the Memorial Sloan-Kettering Cancer Center (1935 to 1976) and 8 from the Connecticut Tumor Registry (1934 to 1976). In addition, 3 previously reported cases from the former institution are updated. Local control was obtained by means of primary radical surgery in 5 of 7 patients, 3 of whom are known to have subsequently died of disseminated disease. One patient initially treated with radical surgery had a local recurrence with metastasis to a regional node, but has now survived for more than 14 years following a second radical surgical procedure. Eight patients were treated primarily with radiotherapy, and 6 have died with metastatic melanoma; another died following pelvic exenteration for persistent local disease. Only 1 patient showed evidence of transient control after radiotherapy, but this patient had a local recurrence 36 months later and died with metastases. The overall 5-year survival rate for these 19 patients was 21%.