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Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries. Standardized incidence ratios (SIRs) with 95% confidence intervals (CI) and cumulative incidence of second malignancies were computed. We observed 175 second malignant neoplasms, yielding a SIR of 4.6, 95% CI: 3.9-5.3. When considering second cancers with at least 10 occurrences, highest relative risks were found for second malignant bone tumors (SIR = 26.4, 16.6-40.0), soft tissue sarcomas (SIR = 14.1, 6.7-25.8) and myeloid leukemia (SIR = 12.7, 6.3-22.8). Significant increased risks for all malignancies combined were observed after sympathetic nervous system tumors (SIR = 11.4, 5.2-21.6), retinoblastomas (SIR = 7.3, 5.4-9.8), renal tumors (SIR = 5.7, 3.8-8.0), malignant bone tumors (SIR = 5.6, 3.7-8.2), soft tissue sarcomas (SIR = 4.7, 3.2-6.8), germ-cell, trophoblastic and other gonadal neoplasms (SIR = 2.5, 1.1-4.9), carcinomas and other malignant epithelial neoplasms (SIR = 2.2, 1.4-3.3). The highest risk of a second malignancy of any type occurred 5 to 9 years after NCNSSC (SIR = 9.9, 6.8-13.9). The cumulative incidence of second malignancies 10 years after the first neoplasm was eight times higher among NCNSSC survivors than in the general population, with the absolute difference between observed and expected cumulative incidence still increasing after 50 years of follow-up. Children who survived a NCNSSC experience a large increased risk of developing a new malignancy, even many years after their initial diagnosis. Copyright © 2011 UICC.

BACKGROUND: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC. METHODS: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC). RESULTS: Among SCC patients, male SIR = 1.58 (95% confidence interval (CI) 1.50-1.66) and female SIR = 2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR = 1.25, 95% CI 1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men. CONCLUSION: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC. British Journal of Cancer (2010) 102, 1190-1195. doi:10.1038/sj.bjc.6605616 www.bjcancer.com (C) 2010 Cancer Research UK

Background: The objective of this study is to assess the risk of second primary cancers following a first primary esophageal cancer as well as the risk of esophageal cancer as a second primary, following first primary cancers of other sites. Methods: The present investigation is a multicenter study of 13 population-based cancer registries in Europe, Australia, Canada, and Singapore. To assess excess occurrence of second cancers after esophageal cancers, we calculated standardized incidence ratios (SIR) by dividing the observed numbers of second cancers by the expected number of cancers calculated from the accumulated person-years and the age-, sex-, calendar period-, and registry-specific first primary cancer incidence rates. Results: During the study period, 959 cases of second primary cancers occurred after an initial esophageal cancer, resulting in a SIR of 1.15 (95% confidence interval, 1.08-1.22). Second primary stomach cancers were associated with first primary esophageal adenocarcinomas (SIR, 2.13; 95% confidence interval, 1.26-3.37) and second primary cancers of the oral cavity and pharynx (6.68; 5.33-8.26), stomach (1.53; 1.14-2.01), larynx (3.24; 1.88-5.18), lung (1.55; 1.28-1.87), kidney (1.88; 1.18-2.85), and thyroid (2.92; 1.18-6.02) were associated with first primary squamous cell carcinomas of the esophagus. An excess of esophageal cancer as a second primary were observed following first primary cancers of the aerodigestive tract, female breast, cervix, testis, bladder, Hodgkin's lymphoma, and non–Hodgkin lymphoma. Conclusion: We observed associations of esophageal cancer with second primary head and neck cancers and lung cancer regardless of years of follow-up, which may suggest that common risk factors play a role in multiple tumor development. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1543–9)

Background: Skin cancers are known to be associated with sun exposure, whereas sunlight through the production of vitamin D may protect against some cancers. The aim of this study was to assess whether patients with skin cancer have an altered risk of developing other cancers. Methods: The study cohort consisted of 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer extracted from 13 cancer registries. 10,886 melanoma and 35,620 non-melanoma skin cancer cases had second cancers. The observed numbers (O) of 46 types of second primary cancer after skin melanoma, basal cell carcinoma or non-basal cell carcinoma, and of skin cancers following non-skin cancers were compared to the expected numbers (E) derived from the age, sex and calendar period specific cancer incidence rates in each of the cancer registries (O/E = SIR, standardised incidence ratios). Rates from cancer registries classified to sunny countries (Australia, Singapore and Spain) and less sunny countries (Canada, Denmark, Finland, Iceland, Norway, Scotland, Slovenia and Sweden) were compared to each other. Results: SIR of all second solid primary cancers (except skin and lip) after skin melanoma were significantly lower for the sunny countries (SIR(S) = 1.03; 95% CI 0.99-1.08) than in the less sunny countries (SIR(L) = 1.14; 95%CI 1.11-1.17). The difference was more obvious after non-melanoma skin cancers: after basal cell carcinoma SIR(S)/SIR(L) = 0.65 (95%CI = 0.58-0.72); after non-basal cell carcinoma SIR(S)/SIR(L) = 0.58 (95%CI = 0.50-0.67). In sunny countries, the risk of second primary cancer after non-melanoma skin cancers was lower for most of the cancers except for lip, mouth and non-Hodgkin lymphoma. Conclusions: Vitamin D production in the skin seems to decrease the risk of several solid cancers (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma, which is consistent with earlier reports that non-melanoma skin cancers reflect cumulative sun exposure, whereas melanoma is more related to sunburn. © 2007 Elsevier Ltd. All rights reserved.

Background: Survivors of childhood leukemia and lymphoma experience high risks of second malignant neoplasms. We quantified such risk using a large dataset from 13 population-based cancer registries. Methods: The registries provided individual data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring in children aged 0-14 years and on subsequent second malignant neoplasms for different time periods from 1943 to 2000. Risks of second malignant neoplasms were assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs), using the incidence rates in the general populations covered by the registries as a reference. Cumulative absolute risks were also calculated. Results: A total of 133 second malignant neoplasms were observed in 16 540 patients (12 731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin lymphomas) after an average follow-up of 6.5 years. The most frequent second malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% CI = 5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% CI = 4.30 to 17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% CI = 8.60 to 35.7); the most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5, 95% CI = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% CI = 7.66 to 45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% CI = 12.5 to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer (six cases, SIR = 40.4, 95% CI = 14.8 to 88.0) and brain cancer (four cases, SIR = 6.97, 95% CI = 1.90 to 17.9). Cumulative incidence of any second malignant neoplasm was 2.43% (95% CI = 1.09 to 3.78), 12.7% (95% CI = 8.29 to 17.2), and 2.50% (95% CI = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, respectively. Conclusions: This population-based study provides, to our knowledge, the most precise and up-to-date estimates for relative and absolute risks of second malignant neoplasms after childhood leukemia and lymphoma. © The Author 2007. Published by Oxford University Press. All rights reserved.

Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor. Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved.

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility. © 2005 Wiley-Liss, Inc.

Cancer of the small intestine is a rare neoplasm, and its etiology remains poorly understood. Analysis of other primary cancers in individuals with small intestine cancer may help elucidate the causes of this neoplasm and the underlying mechanisms. We included 10,946 cases of first primary small intestine cancer from 13 cancer registries in a pooled analysis. The observed numbers of 44 types of second primary cancer were compared to the expected numbers derived from the age-, gender- and calendar period-specific cancer incidence rates in each registry. We also calculated the standardized incidence ratios (SIR) for small intestine cancer as a second primary after other cancers. There was a 68% overall increase in the risk of a new primary cancer after small intestine carcinoma (SIR = 1.68, 95% confidence interval [CI] = 1.47-1.71), that remained constant over time. The overall SIR was 1.18 (95% CI = 1.05-1.32) after carcinoid, 1.29 (1.01-1.63) after sarcoma, and 1.27 (0.78-1.94) after lymphoma. Significant (p < 0.05) increases were observed for cancers of the oropharynx, colon, rectum, ampulla of Vater, pancreas, corpus uteri, ovary, prostate, kidney, thyroid gland, skin and soft tissue sarcomas. Small intestine cancer as a second primary was increased significantly after all these cancers, except after oropharyngeal and kidney cancers. Although some of the excess may be attributable to overdiagnosis, it is plausible that most additional cases of second primary cancers were clinically relevant and were due to common genetic (e.g., defects in mismatch or other DNA repair pathways) and environmental (e.g., dietary) factors. © 2005 Wiley-Liss, Inc.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. 1294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx, and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at higher age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74, and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.Impact statementWhile the incidence of first primary cancers of the head and neck increases with advancing age that of second primary cancers is stable between age 40 and 70 and, if anything, declines thereafter.

The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a PC. The present investigation is a multicenter study from 13 population-based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person-years and the age, sex- and calendar period-specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking. (C) 2008 Wiley-Liss, Inc.

Purpose: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. Methods: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. Results: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). Conclusion: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour. © 2008 Elsevier Ltd. All rights reserved.

We investigated the risk of second malignancies among 29,511 survivors of germ-cell testicular cancer recorded in 13 cancer registries. Standardized incidence ratios (SIRs) were estimated comparing the observed numbers of second malignancies with the expected numbers obtained from sex-, age-, period- and population-specific incidence rates. Seminomas and nonseminomas, the 2 main histological groups of testicular cancer, were analyzed separately. During a median follow-up period of 8.3 years (0-35 years), we observed 1,811 second tumors, with a corresponding SIR of 1.65 (95% confidence interval (CI): 1.57-1.73). Statistically significant increased risks were found for fifteen cancer types, including SIRs of 2.0 or higher for cancers of the stomach, gallbladder and bile ducts, pancreas, bladder, kidney, thyroid, and for soft-tissue sarcoma, nonmelanoma skin cancer and myeloid leukemia. The SIR for myeloid leukemia was 2.39 (95% CI: 1.41-3.77) after seminomas, and 6.77 (95% CI: 4.14-10.5) after nonseminomas. It increased to 37.9 (95% CI: 18.9-67.8; based on 11 observed cases of leukemia) among nonseminoma patients diagnosed since 1990. SIRs for most solid cancers increased with follow-up duration, whereas they did not change with year of testicular cancer diagnosis. Among subjects diagnosed before 1980, 20 year survivors of seminoma had a cumulative risk of solid cancer of 9.6% (95% CI: 8.7-10.5%) vs. 6.5% expected, whereas 20 years survivors of non-seminoma had a risk of 5.0% (95% CI: 4.2-6.0%) vs. 3.1% expected. In conclusion, survivors of testicular cancers have an increased risk of several second primaries, where the effect of the treatment seems to play a major role. © 2006 Wiley-Liss, Inc.

Ocular melanoma is a rare neoplasm with a poorly understood etiology, especially concerning its link with ultraviolet-light exposure. Studying the risk of second primary cancers may help to formulate causal hypotheses. We used data from 13 cancer registries, including 10,396 first occurring ocular melanoma cases, and 404 second occurring cases. To compare the second cancer incidence in ocular melanoma patients to that in noncancer population, we calculated standardized incidence ratios (SIRs) of 32 types of cancer. We also calculated SIRs of second ocular melanoma after other primaries. Ocular melanoma patients had significantly increased risk of cutaneous melanoma (SIR = 2.38, 95% CI 1.77-3.14), multiple myeloma (SIR = 2.00, 1.29-2.95), and of liver (SIR = 3.89, 2.66-5.49), kidney (SIR = 1.70, 1.22-2.31), pancreas (SIR = 1.58, 1.16-2.11), prostate (SIR = 1.31, 1.11-1.54), and stomach (SIR = 1.33, 1.03-1.68) cancers. Risks of cutaneous melanoma were highly variable between registries and were mainly increased in females, in younger patients, in first years following diagnosis, and for patients diagnosed after 1980. The risk of ocular melanoma was significantly increased only after prostate cancer (SIR = 1.41, 1.08-1.82). Risk of cutaneous melanoma after ocular melanoma had epidemiological patterns, similar to cutaneous melanoma screening in the general population. The increased risk of cutaneous melanoma would be largely due to greater skin cancer surveillance in ocular melanoma patients, and not to common etiological factors. The high SIR found for liver cancer may be explained by misclassification bias. Common etiological factors may be involved in ocular and prostate cancers. © 2006 Wiley-Liss, Inc.

Objective: To study the risk of second primary cancers in nasopharyngeal carcinoma (NPC) patients and the risk of NPC as second primary cancer. Methods: We used data from the cancer registries from Singapore and from 12 low-incidence areas, including a total of 8,947 first occurring NPC cases, and 167 second occurring cases. We calculated standardized incidence ratios (SIRs) by comparing the second cancer incidence in NPC patients to the first primary cancer incidence in non-cancer population. We also calculated SIRs of second NPC after other primaries. Results: In Singapore, the risk of cancers of the lung (SIR = 0.42), stomach (SIR = 0.41), and colon (SIR = 0.23) was significantly decreased after NPC, whereas that of cancer of the tongue (SIR = 11.1) was significantly increased. In Australia, Canada, and Europe, the risk of non-Hodgkin's lymphoma (NHL) (SIR = 3.06), tongue cancer (SIR = 5.29), brain cancer (SIR = 3.89), myeloid leukemia (SIR = 3.85), and non-melanoma skin cancer (NMSC) (SIR = 3.47) was significantly increased after NPC. Incidences of second occurring NPCs following various primary cancers were not significantly altered compared to the incidence of first occurring NPCs. Conclusions: Immune suppression (NHL, NMSC), shared genetic factors (lung cancer, NHL, myeloid leukemia), and shared environmental risk factors (tongue and brain cancers) might explain the associations. Except for NHL, there was no evidence of association with other Epstein-Barr virus-related cancers. © 2007 Springer Science+Business Media B.V.

Context: Increasing incidence and improved prognosis of thyroid cancer have led to concern about the development of second primary cancers, especially after radioiodine treatment. Thyroid cancer can also arise as a second primary neoplasm after other cancers. Objective: The objective of the study was to assess the risk of second primary cancer after thyroid cancer and vice versa. Design: This was a multinational record linkage study. Setting: The study was conducted at 13 population-based cancer registries in Europe, Canada, Australia, and Singapore. Patients or Other Participants: A cohort of 39,002 people (356,035 person-yr of follow-up) with primary thyroid cancer were followed up for SPN for up to 25 yr, and 1,990 cases of thyroid cancer were diagnosed after another primary cancer. Main Outcome Measures: To assess any possible excess of second primary neoplasms after thyroid cancer, the observed numbers of neoplasms were compared with expected numbers derived from age-, sex-, and calendar period-specific cancer incidence rates from each of the cancer registries, yielding standardized incidence ratios (SIRs). The SIR of second primary thyroid cancer after various types of cancer was also calculated. Results: During the observation period, there were 2821 second primary cancers (all sites combined) after initial diagnosis of thyroid cancer, SIR of 1.31 (95% confidence interval 1.26–1.36) with significantly elevated risks for many specific cancers. Significantly elevated risks of second primary thyroid cancer were also seen after many types of cancer. Conclusion: Pooled data from 13 cancer registries show a 30% increased risk of second primary cancer after thyroid cancer and increased risks of thyroid cancer after various primary cancers. Although bias (detection, surveillance, misclassification) and chance may contribute to some of these observations, it seems likely that shared risk factors and treatment effects are implicated in many. When following up patients who have been treated for primary thyroid cancer, clinicians should maintain a high index of suspicion for second primary cancers.