Increased stomach cancer risk following radiotherapy for testicular cancer.

BACKGROUND: Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose-response relationship are sparse. METHODS: In a cohort of 22,269 5-year TC survivors diagnosed during 1959-1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression. RESULTS: Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7-20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose (P-trend<0.001), with an OR of 20.5 (3.7-114.3) for ⩾50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated ⩾20 years after exposure (P<0.001). Risk after any chemotherapy was not elevated (OR=1.1; 95% CI 0.5-2.5; 14 cases and 23 controls). CONCLUSIONS: Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of ⩾30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.

Pancreatic cancer risk after treatment of Hodgkin lymphoma.

BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.

Risk of treatment-related esophageal cancer among breast cancer survivors.

BACKGROUND: Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. DESIGN: Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. RESULTS: The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). CONCLUSIONS: Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Relationship of leukemia risk to radiation dose following cancer of the uterine corpus.

BACKGROUND: Radiotherapy has been linked infrequently to secondary leukemia despite extensive exposure of the active bone marrow to ionizing radiation. Few studies include substantial numbers of elderly patients. PURPOSE: We evaluated women with cancer of the uterine corpus, the majority of whom were treated at older ages, to gain additional information on cancer risk following partial-body radiotherapy and to examine differences in risk between external-beam therapy and brachytherapy. METHODS: A cohort of 110,000 women with invasive cancer of the uterine corpus who survived at least 1 year following their initial cancer was assembled from nine population-based cancer registries. Cancer diagnoses occurred from 1935 through 1985, and most patients were diagnosed during the 1960s and 1970s. Radiation doses were computed to 17 sections of the active bone marrow for 218 women who developed leukemia and for 775 matched control subjects. RESULTS: Radiotherapy did not increase the risk of chronic lymphocytic leukemia (CLL) (relative risk [RR] = 0.90; 95% confidence interval [CI] = 0.4-1.9). However, for all leukemias except CLL, a significant risk was identified (RR = 1.92; 95% CI = 1.3-2.9). Overall, the pattern of risk in relation to dose was erratic and was most consistent with a constant increased risk across the entire dose range. The risk following continuous exposures from brachytherapy at comparatively low doses and low dose rates (RR = 1.80; 95% CI = 1.1-2.8; mean dose = 1.72 Gy) was similar to that after fractionated exposures at much higher doses and higher dose rates from external-beam treatment (RR = 2.29; 95% CI = 1.4-3.7; mean dose = 9.88 Gy), indicating a large difference in the estimated risk per unit dose. Risk did not vary by age at first exposure; increased risks were apparent for irradiated patients aged 65 years or older (RR = 1.77; 95% CI = 0.9-3.5). CONCLUSION: The leukemia risk associated with partial-body radiotherapy for uterine corpus cancer was small; about 14 excess leukemia cases were due to radiation per 10,000 women followed for 10 years. Women aged 65 years or older had a radiation risk comparable with that found in younger women. The relationship of leukemia risk to radiation dose was found to be complex due to the competing processes of cell killing, transformation, and repair. At very high doses delivered at high rates, destruction of cells likely dominates, and the risk per unit dose is low. In the low dose range, where dose was protracted and delivered at relatively low dose rates, the leukemia risk appears lower than that projected from risk estimates derived from the instantaneous whole-body exposures of atomic bomb survivors.

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

Risk of subsequent malignant neoplasms among 1,641 Hodgkin's disease patients diagnosed in childhood and adolescence: a population-based cohort study in the five Nordic countries. Association of the Nordic Cancer Registries and the Nordic Society of Pediatric Hematology and Oncology.

PURPOSE: To assess the risk of subsequent malignant neoplasms among Hodgkin's disease patients diagnosed before 20 years of age in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). PATIENTS AND METHODS: There were 1,641 Hodgkin's disease patients identified through the national cancer registries since the 1940s or 1950s. The patients were monitored for 17,000 person-years until the end of 1991. Expected figures were derived from the age-specific incidence rates in each country and standardized incidence ratios (SIR) were calculated. RESULTS: A total of 62 subsequent neoplasms were diagnosed (SIR, 7.7; 95% confidence interval [CI], 5.9 to 9.9). The overall cumulative risk of subsequent neoplasms was 1.9% at the 10-year follow-up point, 6.9% at 20 years, and 18% at 30 years. There were 26 subsequent neoplasms among males (SIR, 6.5; 95% CI, 4.3 to 9.6) and 36 among females (SIR, 8.9; 95% CI, 6.2 to 12), of which 16 were breast cancers (SIR, 17; 95% CI, 9.9 to 28). High risks were seen for thyroid cancer (SIR, 33; 95% CI, 15 to 62), for secondary leukemia (SIR, 17; 95% CI, 6.9 to 35), and for non-Hodgkin's lymphoma (SIR, 15; 95% CI, 4.9 to 35). The relative risk increased from 3.3 (95% CI, 1.2 to 7.1) for Hodgkin's disease patients diagnosed in the 1940s and 1950s to 15 (95% CI, 7.4 to 27) in the 1980s. The highest risk of secondary leukemia (SIR, 68; 95% CI, 18 to 174) was seen among those diagnosed with Hodgkin's disease in the 1980s. CONCLUSION: Patients who survive Hodgkin's disease at a young age are at very high relative risk of subsequent malignant neoplasms throughout their lives. In particular, the high relative risk of breast cancer following Hodgkin's disease in the teenage years calls for enhanced activity for early diagnosis.

Quality of prostate cancer data in the cancer registry of Norway.

Completeness of reporting and internal validity of the coding of prostate cancer in the Cancer Registry (CR) in Norway were examined. Data were matched and evaluated against diagnostic indices at eight selected hospitals in the country and against death certificates from Statistics Norway. Validity control was based on detailed re-analysis of an approximately 1% sample of the registered data during the period 1957-1986. The deficiency in reporting of prostate cancer was less than 1%. The grave deficiencies in hospital patient registers were considered to be of non-systematic nature and should, therefore, not impair the reliability of our investigation of incompleteness. The validity control revealed errors in 0.5% of the data elements, or, illustrated differently, 6% of the patient files had an error, of importance or not, in one of the data elements. One false positive registration was found among 298 controlled patient files (0.3%).

Cancer of the prostate in Norway 1957-1991--a descriptive study.

The incidence and mortality of prostate cancer from 1957 to 1991 were studied in the Cancer Registry of Norway. The age-adjusted incidence rate increased from 26.3 to 46.6 per 100,000 person-years during the period, and more than 2000 cases are now registered yearly. The increase tends to be higher in the younger age groups, 50-59 years, and among the oldest, 90+ years. An increase was also found in cause-specific mortality, signifying a real increase in incidence over time. There is a slight urban dominance in incidence of prostate cancer. Autopsy findings account for less than 1.7% of the total. The histo- and cytological verification rate reached 94% in 1987-1991 and the percentage of localised cases was 68.4%. The median age at diagnosis in 1987-1991 was 75.1 years. Data on stage at time of diagnosis, histological differentiation and survival, reflect a small influence of earlier diagnosis. Model analysis revealed no particular birth cohort effect, either on incidence or on mortality.

Cause of death and long-term survival in patients with neuro-epithelial brain tumours: a population-based study.

Long-term survivors of neuro-epithelial brain tumours have a higher death rate compared with the general population and the aims of this study were to investigate the causes of death and analyse long-term survival using population-based material. A total of 6209 patients were registered in the period of 1970-1993 with a primary intracranial neuro-epithelial tumour in the The Norwegian Cancer Registry. In a pilot study, a high level of agreement with regard to the cause of death was found between clinical data and the registered cause of death. Underlying causes of death in the whole population were therefore analysed. Most deaths were caused by the primary neuro-epithelial brain tumour within 10 years of diagnosis. Although the numbers were small, the proportion of patients dying from other cancers, vascular disease, infections and accidents continued to rise with time. Survival was computed using the Kaplan-Meier method. For children, survival at 5, 10 and 15 years significantly improved from the time period of 1970-1981 to 1982-1993 (47.9, 43.6 and 43.3% versus 63.8, 59.8 and 59.8%, respectively, P <0.0001). Similar improvements in survival at 5, 10 and 15 years were observed for young adults aged 15-49 years (32.7, 21.3 and 16.5% versus 50.1, 37.5 and 33.1%, for the same time periods, P<0.0001). No such improvement for those aged 50 years and over was observed (corresponding figures of 6.6, 3.8 and 2.8% versus 7.7, 4.8 and 3.4%). Prognosis for those with childhood medulloblastomas improved significantly, as did the prognosis of younger adults with low-grade gliomas and unbiopsied/ unclassifiable grade gliomas.

Colorectal cancer survival trends in Norway 1958-1997.

The purpose of this study was to examine the pattern of survival for colorectal adenocarcinoma (CRC), and to investigate the prognostic factors for the disease. In the analysis, 50993 cases of CRC aged 40-84 years, diagnosed between 1958 and 1997 in Norway, were included. Esteve's relative survival method was used, together with a time trend analysis, conducted by least-squares linear regression. Cox proportional hazards regression analysis was used to examine cause-specific mortality. Five-year relative CRC survival has increased by an estimated 3% per 5-year diagnostic period. In 1958-1962, relative survival was about 40% for both males and females, and increased to 56 and 60%, respectively, in 1993-1997. Rectal cancer had a higher cause-specific mortality (RR 1.26, 95% CI 1.22-1.30) than proximal colon (reference) and distal colon (RR 0.97, 95% CI 0.93-1.00 cancers), while females had a lower cause-specific mortality than males (RR 0.88, 95% CI 0.86-0.90). The increase in the relative survival rate in Norway is probably due to improved treatments and advanced diagnostics. Norway has a higher CRC survival rate than the EUROCARE average.

Neoplasms of the central nervous system in Norway. II. Descriptive epidemiology of intracranial neoplasms 1955-1984.

A population-based study of 8480 patients - 4508 (53%) males and 3972 females - with primary intracranial neoplasms reported to the Norwegian Cancer Registry during the period 1955-84, is presented. 81% of the cases were histologically verified. The peak age-specific incidence rate in the total series occurred in the age-group 55-64 years. Gliomas constituted the largest histological group with an age-adjusted incidence rate of 5.0 cases per 100,000 population per year for males and 3.5 for females. Case ascertainment of primary intracranial neoplasms is reduced above the age of 60 in Norway, mostly due to a a low autopsy rate. The major impact of the introduction of computer tomography (CT) in the case ascertainment of intracranial neoplasms has been a raised incidence, in patients over the age of 60, of neoplasms which are not histologically verified.

Neoplasms of the central nervous system in Norway. I. Quality control of the registration in the Norwegian Cancer Registry.

The Norwegian Cancer registry includes reports on 8,933 cases of primary central nervous system neoplasms diagnosed in the period 1955-1984. Before submitting this data set to epidemiological analysis, errors were searched out and subsequently corrected, and a quality control was performed. First, seven categories of neoplasm records likely to be faulty were defined. In this way 109 cases (1.2% of the total) were identified for extensive study. Minor or major errors were found and corrected in 86 cases. The main source of error was misinterpretation of data by cancer registry staff (67 out of 109 cases). The second approach was to evaluate the quality of the corrected data set by a random draw of 300 cases. Errors concerning total incidence rates and rates for main groups of gliomas, meningiomas and neurilemmomas represented 0.3% of the total, and altogether 9.3% of errors of varying severity were revealed. The series is discussed with regard to prerequisites for serving as reliable data on CNS neoplasm epidemiology. The results indicate that the data from the Norwegian Cancer Registry is sufficiently valid for a thorough study of CNS neoplasms.

Head and neck cancer in Norway. A study of the quality of the Cancer Registry of Norway's data on head and neck cancer for the period 1953-1991.

Data from population-based cancer registries provide information on the causes and outcome of cancer and form a basis for important decision making in connection with the prevention of cancer and the planning of health services. This makes it of the utmost importance to assess the data at all stages of collection to ensure the highest possible quality. The present study focuses on the quality of the Cancer Registry of Norway's data on head and neck cancer for the period 1953-1991. When the study was started, 16,104 cases of head and neck malignancies had been registered. All histological codes were reviewed. The pathologists' reports were reevaluated for 369 cases selected according to set criteria: 133 cases received a new histological code without being excluded from the data material: 112 cases were excluded. The distribution of histological diagnoses for each location is presented. A reevaluation of 300 cases selected at random from the corrected series indicates discrepancies between the pathologist's classification and the Registry's coding in less than 2% (1.4%) of all cases. The percentage that lacked histological verification fell from 5.7% in the first decade to 2.1% during the last 9-year period. Completeness of the Cancer Registry's data base was checked against hospital-based registries and this investigation showed that virtually all new cases are reported. We conclude that the data on head and neck cancer for the studied time period meet standards that justify their use as a basis for epidemiological as well as clinical studies.

Circulating secretory component in relation to early diagnosis and treatment of liver metastasis from colorectal carcinomas.

AIMS: To evaluate serum secretory component in relation to early detection and clinical management of liver metastasis in patients with colorectal cancer. METHODS: Secretory component and carcinoembryonic antigen (CEA) were analysed in serial serum samples from 23 patients who had liver metastases as the only apparent recurrence, and in sera from 54 matched controls. Results of surgical treatment of recurrences were classified peroperatively as radical when no residual tumour was apparent and resection margins were free of disease. RESULTS: In total, 18 (78%) patients had increased secretory component during the whole follow up period (median 16 months); 12 (52%) had raised secretory component concentrations before clinical recurrence (median lead time 5.2 months). There was no difference before recurrence between circulating secretory component and CEA in sensitivity and lead times. Seventeen patients underwent surgery for hepatic metastasis; seven had radical hepatic resection of which only two (29%) showed increased secretory component concentrations before clinical recurrence; both had concurrent raised CEA values. By contrast, secretory component was raised in 83% of those cases considered inoperable. CONCLUSIONS: Although serum secretory component clearly increases in most patients with liver metastases, its clinical value seems questionable because secretory component apparently indicates mainly inoperable hepatic metastases.

Trends in colorectal cancer incidence in Norway by gender and anatomic site: an age-period-cohort analysis.

The purpose of this study was to examine the secular trend of colorectal cancer in Norway by gender and subsite. All new cases of cancer in proximal colon, distal colon and rectum diagnosed between 1958 and 1997 in Norway were included in the study, altogether 34 202 and 34 097 cases for men and women, respectively. The incidence data were fitted separately for each gender and subsite to an age-period-cohort model. An increase in incidence of colorectal cancer was seen from 1958 to 1997 for both men and women, although a moderate attenuation of the increase has taken place in the last 15-20 years. This observation is most pronounced for cancer of the distal colon, but is also evident for proximal colonic and rectal cancers. For the distal colon and rectum, the period effect is more important than the cohort effect for both genders, whilst opposite for the proximal colon. The main estimated trend for cohort effects is a steady increase for both men and women, apart from an unexpected drop in incidence among the cohorts born during or shortly after World War II. These findings indicate that different aetiological risk factors may act on cancers of the proximal and distal part of the large bowel and further suggest that exogenous risk factors acting very early in life may play a more important role for colorectal cancer than previously recognized.

Erythrocyte sedimentation rate as a prognostic factor in renal cell carcinoma.

In a follow-up study of 193 adult patients with renal cell carcinoma diagnosed in northern Norway 1974-1980, ESR as a prognostic factor was studied with the Cox regression model. In 71 patients (37%) metastatic disease was known at diagnosis. In patients without metastatic disease an elevated ESR greater than 15 mm/h and renal vein involvement were significant prognostic factors indicating short survival. Multivariate survival analyses of all patients showed the presence of metastatic disease and elevated ESR (greater than 15 and greater than 30 mm/h) as significant prognostic factors indicating high-risk patients. This study concludes that ESR deserves attention as a prognostic discriminator in renal cell carcinoma.

Comparison of lipid status in the hearts of piglets and rats on short term feeding of marine oils and rapeseed oils.

A series of 4 experiments with piglets and one experiment with rats has been conducted to establish the cardiac lipid status of weanling (3 weeks old) male animals fed fats with different contents of docosenoic fatty acids. Experimental fats were rapeseed oil (RSO) (48.0% 22:1), refined fish oil (RFO) (14.6% 22:1), partially hydrogenated fish oil (PHFO) (14.3% 22:1) and lard (0% 22:1) combined with sunflower seed oil (SFO) in different proportions in diets with 21% total fat. Lipidosis could not be detected in piglets as increased heart weights, by chemical assay for myocardial contents of triglycerides, or by accumulation of docosenoic fatty acids or nonesterified fatty acids (NEFA). In rats, diets with RSO at a level of 16% increased myocardial triglyceride and docosenoic fatty acid contents about 7 times while the effect on cardiac NEFA was inconsistent. Histological examinations of the hearts revealed stainable intracellular fat droplets in some piglets fed 16% RSO for 8 to 13 days, but not after 2, 4 and 6 and 16, 19 and 22 days of feeding. After 10 days of feeding, mild to moderate histological lipidosis was found in piglets fed diets containing 2% or more of 22:1 fatty acids, with no significant difference between RSO, RFO and PHFO in this respect. The same diets in rats gave about 5 times more histological lipidosis than in piglets. This is attributed to a difference in species response, the rat reacting in a more pronounced manner than the piglet. The cardiac lipidosis no-effect level in piglets corresponded to a daily intake of docosenoic fatty acids of 0.4 g per kg body weight. Mild lipidosis was also found in a few animals on docosenoic acid-free diets.

Incidence of cancer in the mineral-wool producing industry in Norway.

This study concerned the Norwegian phase of a European collaborative investigation on workers in man-made mineral fiber production. A study population of 2,361 men from four Norwegian plants was examined for mortality and cancer incidence, especially lung cancer, based on a comparison of observed and expected figures, the latter determined according to the five-year age-specific mortality and incidence rates for the entire country. Violent deaths among workers with less than one year of employment represented the only significant mortality excess. A borderline, statistically significant excess risk was found for cancer of the buccal cavity and pharynx, but the fact that the excess occurred in one factory only led to the assumption that the risk was associated with factors other than mineral wool. An excess risk for lung cancer was also found among those with 20 years or more since first exposure (9 observed and 4.36 expected). The risk that emerged was presumably initiated before 1960, when the environmental conditions were more hazardous than later.

Congenital diaphragmatic hernia: the hidden mortality.

From 1969 to 1975, 33 cases of congenital diaphragmatic hernia (CDH) were treated at the National Hospital of Norway with a "visible" or operative mortality of 30%. At least 37 additional infants with CDH who died soon after birth and did not come to the attention of a major referral center were identified retrospectively from a comprehensive survey of neonatal deaths. CDH occurred at least once in every 5455 live births and the "true" mortality was 66%. More than half of the infants born with CDH during this 6-yr period died before they could be treated, contributing to a substantial "hidden" mortality.

Assessment of fine needle aspiration cytology and histopathology for diagnosing male breast masses.

OBJECTIVE: To investigate the diagnostic accuracy of fine needle aspiration cytology (FNAC) from breast lesions in males and to determine the frequency of benign versus malignant histopathologic diagnoses in surgical biopsies from male breast lesions. STUDY DESIGN: FNAC specimens from breast lesions taken from 241 males over 8.5 years were divided into four subgroups according to the original cytologic diagnoses. Diagnostic accuracy was verified with the Norwegian Cancer Registry. Ten years' worth of material from 809 surgical biopsies from male breast lesions was subgrouped according to the original histopathologic diagnoses. RESULTS: Of the 809 surgical biopsies, 779 (96.3%) were benign lesions. Of the 241 fine needle aspirates, 27 (11.2%) were unsatisfactory for cytologic diagnosis. Of the remaining 214 cases, 200 benign cytologic diagnoses were confirmed at follow-up. Thus, there were no false negative cytologic diagnoses; eight malignant diagnoses were confirmed by later histopathologic examination of the surgical biopsy. CONCLUSION: To reduce the high rate of surgical biopsies of benign male breast masses, we conclude that FNAC should be performed as a standard procedure in the clinical evaluation of male breast lesions.