Multiple cancer prevalence: a growing challenge in long-term survivorship.

OBJECTIVE: The present study was designed to estimate the number of and describe the pattern of disease among cancer survivors living with a history of multiple malignant tumors in the United States. METHODS: Incidence and follow-up data from the Surveillance, Epidemiology, and End Results program (1975-2001) were used to calculate the number of survivors with more than one malignant primary at January 1, 2002. U.S. prevalence counts were calculated by multiplying the age, sex, and race-specific prevalence proportions from the Surveillance, Epidemiology, and End Results program by the corresponding U.S. populations. RESULTS: We estimate that 756,467 people in the United States have been affected by cancer more than once between 1975 and 2001, representing almost 8% of the current cancer survivor population. Women whose first primary in that period was breast cancer represent 25% of survivors with multiple cancers, followed by men and women (15%) whose first primary was colorectal cancer and men (13%) whose first primary was prostate cancer. DISCUSSION: The findings in this report have important implications for public health practice. With individuals diagnosed with cancer living longer and the aging of the U.S. population, the number who will develop multiple malignancies is expected to increase. As a consequence, there is a growing need to promote effective cancer screening along with healthy life-styles among these at-risk populations if we are to ensure optimal physical and psychosocial well-being of these long-term cancer survivors and their families. Efforts to design and evaluate effective, efficient, and equitable approaches to surveillance for second malignancies will be critical in reducing the national burden of cancer.     

New malignancies following childhood cancer in the United States, 1973-2002

The objectives of our study were to quantify risks for developing new malignancies among childhood cancer survivors, identify links between particular types of first and subsequent cancer, and evaluate the possible role of treatment. A cohort of 25,965 2-month survivors of childhood cancer diagnosed in the U.S. during 1973-2002 was identified and followed through SEER cancer registries. Observed-to-expected ratios (O/E) were calculated, and Poisson regression was used to compare risks among treatment groups. Childhood cancer survivors were at nearly 6-fold risk of developing a new cancer relative to the general population (O/E = 5.9, 95% CI: 5.4-6.5). Most common were subsequent primary cancers of the female breast, central nervous system, bone, thyroid gland and soft tissue, as well as cutaneous melanoma and acute non-lymphocytic leukemia (ANLL). The greatest risks of subsequent cancers occurred among patients diagnosed previously with Hodgkin lymphoma (HL), Ewing sarcoma, primitive neuroectodermal tumor, or retinoblastoma. Risk of subsequent solid cancers was higher among persons whose initial treatment for childhood cancer included radiotherapy, whereas the excess of subsequent ANLL was strongly related to chemotherapy. The O/E for subsequent ANLL increased with increasing calendar year of initial cancer diagnosis among survivors of cancers other than HL, most likely due to increasing use of leukemogenic drugs for solid cancers and non-Hodgkin lymphoma. Childhood cancer survivors are at markedly increased risk of developing a variety of new cancers relative to the general population, but the magnitude of excess risk and specific types of second cancer vary widely by type of first cancer.     

Survivorship care for older adults with cancer: U13 conference report

Older adult cancer survivors currently account for almost 60% of all cancer survivors. The number of older cancer survivors will continue to increase as the population ages and as patients' live longer after a cancer diagnosis. As part of cancer center accreditation, the American College of Surgeons Commission on Cancer® (CoC) has placed great importance on survivorship care planning. While the CoC has set standards for general survivorship care, there is sparse evidence on how to best care for older adult cancer survivors. Concern exists among the medical community that survivorship care plans could increase paperwork without improving outcomes. Given the diverse and unique needs of older adult cancer survivors, the inter-professional team provides a structure and process for survivorship care built around the particular needs of older adults. The Cancer and Aging Research Group (CARG), in partnership with the NIA/NCI, held a U13 conference in May 2015 in part to discuss survivorship care for older adults with cancer. This report discusses four themes that emerged from one section of the conference: (1) survivorship care is a process that continually evolves to meet the needs of older adults; (2) older adult cancer survivors have unique needs and care plans should be tailored to meet these needs; (3) the inter-professional team is ideally suited to structure survivorship care of older adults; (4) patient advocacy must be encouraged throughout the cancer care continuum. As evidence based survivorship practices develop, the unique needs of older adults need to be given substantial attention.     

Late effects in survivors of teenage and young adult cancer: does age matter?

BackgroundLate effects (LEs) after cancer treatment are increasing. After childhood cancer, substantial risks include physical, psychological and social LE and vary with age. Teenagers and young adults (TYA) present with particular cancers; their risk of LE may relate to cancer site, treatment or their age itself. The LEs after TYA-onset cancers are described in relation to age at diagnosis of primary tumour.Patients and methodsData were extracted from Medline English language articles, 1999–2009. Keywords were late effect/s, late toxicity and survivor and the frequent TYA cancer sites. Only those articles that reported the relation between LEs risks with age at diagnosis were included.ResultsThe majority of known LEs are described after TYA cancer. No study primarily aimed to relate TYA age to LEs. Many studies did not report LE by age. TYA-specific risks are seen in cardiac toxicity, second malignancies, pulmonary complications and psychosocial difficulties when compared with older or younger cancer survivors.ConclusionsTYA age brings specific LE risks after cancer. Prospective population-based collection of LE data after TYA cancer will inform the development of appropriate services to effectively manage LE.     

Identifying and screening patients at risk of second cancers.

BACKGROUND: The average age of the U.S. population is increasing, and cancer incidence increases with age. Both improved early detection of first malignancies and effective primary oncologic therapy have led to prolonged survival, and the risk of secondary malignancies has consequently increased. A few anatomic sites are at increased risk for second malignancies within the same organ: breast, colon and rectum, lung, head and neck (or upper aerodigestive malignancies), prostate, and the uterine cervix. Some of the cancers also incur a risk for a second malignancy at another anatomic site. In addition, there are well-described clinical genetic syndromes that, as unique clinical entities, predispose to second malignant tumors. METHODS/RESULTS: In this review, we focus on issues related to the risk of second malignancies among patients with primary breast, colon, lung and head and neck, prostate, and cervical cancers that comprise the most common sites of primary malignancy among patients in the United States. We review recent data related to both established and new screening strategies at these sites. CONCLUSIONS: There is some evidence that screening will improve outcomes among patients who may develop second malignancies, although the data are limited. The optimal screening modalities and strategies to reduce mortality from second malignancies remain to be defined for most tumor sites.     

Clinical trials in older adults with cancer: past and future

The risk of cancer increases with age, and as the U.S. population rapidly ages, the number of older adults seeking treatment for cancer is also increasing dramatically. However, this growing population of older adults has been underrepresented in clinical trials that set the standards for oncology care. In addition, most clinical trials conducted to date have not addressed the problems that accompany aging, including reduced physiologic reserve, changes in drug pharmacokinetics, and the impact of comorbid medical conditions and polypharmacy on treatment tolerance. As a result, there are variations in treatment patterns between older and younger adults and few evidence-based guidelines accounting for the changes in physiology or pharmacokinetics that occur with aging. This article examines the demographics of cancer and aging, the barriers to enrollment of older adults on clinical trials, and approaches for future trials to address the needs of the older patient.     

Second primary cancers: an overview.

Substantial improvements in the past few decades in cancer detection and supportive care along with advances in therapy have led to growing numbers of cancer survivors. In view of the prolongation of survival in increasing numbers of patients, identification and quantification of the late effects of cancer and its therapy have become critical. One of the most serious events experienced by cancer survivors is the diagnosis of a new cancer. The number of patients who have second or higher-order cancers is increasing, and solid tumors are a leading cause of mortality among several populations of long-term survivors, including patients who have Hodgkin lymphoma. The focus of this article is treatment-associated malignancies in survivors of selected adult cancers.     

Trends in the risk and burden of second primary malignancy among survivors of smoking-related cancers in the United States

While there are a growing number of cancer survivors, this population is at increased risk of developing second primary malignancies (SPMs). We described the incidence, most common tumor sites, and trends in burden of SPM among survivors of the most commonly diagnosed smoking-related cancers. The current study was a population-based study of patients diagnosed with a primary malignancy from the top 10 smoking-related cancer sites between 2000 and 2014 from Surveillance, Epidemiology, and End Results data. SPM risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). Trends in the burden of SPM were assessed using Joinpoint regression models. A cohort of 1,608,607 patients was identified, 119,980 (7.5%) of whom developed SPM (76% of the SPMs were smoking-related). The overall SIR of developing second primary malignancies was 1.51 (95% CI, 1.50–1.52) and the EAR was 73.3 cases per 10,000 PYR compared to the general population. Survivors of head and neck cancer had the highest risk of developing a SPM (SIR = 2.06) and urinary bladder cancer had the highest excess burden (EAR = 151.4 per 10,000 PYR). The excess burden of SPM for all smoking-related cancers decreased between 2000 and 2003 (annual percentage change [APC] = −13.7%; p = 0.007) but increased slightly between 2003 and 2014 (APC = 1.6%, p = 0.032). We show that 1-in-12 survivors of smoking-related cancers developed an SPM. With the significant increase in the burden of SPM from smoking-related cancers in the last decade, clinicians should be cognizant of long-term smoking-related cancer risks among these patients as part of their survivorship care plans.     

Risk of second non-hematological malignancies among 376,825 breast cancer survivors

Breast cancer survivors are at increased risk of treatment-related second cancers. This study is the first to examine risk 30 or more years after diagnosis and to present absolute risks of second cancer which accounts for competing mortality. We identified 23,158 second non-hematological malignancies excluding breast in a population-based cohort of 376,825 one-year survivors of breast cancer diagnosed from 1943 to 2002 and reported to four Scandinavian cancer registries. We calculated standardized incidence ratios (SIR) and utilized a competing-risk model to calculate absolute risk of developing second cancers. The overall SIR for second cancers was 1.15 (95% confidence interval [CI] = 1.14–1.17). The SIR for potentially radiotherapy-associated cancers 30 or more years after breast cancer diagnosis was 2.19 (95% CI = 1.87–2.55). However, the largest SIRs were observed for women aged <40 years followed for 1–9 years. At 20 years after breast cancer diagnosis, the absolute risk of developing a second cancer ranged from 0.6 to 10.3%, depending on stage and age; the difference in the absolute risk compared to the background population was greatest for women aged <40 years with localized disease, 2.3%. At 30 years post breast cancer diagnosis, this difference reached 3.2%. These risks were small compared to the corresponding risk of dying from breast cancer. Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease.     

Differences in smoking prevalence and eligibility for low-dose computed tomography (LDCT) lung cancer screening among older U.S. adults: role of sexual orientation

The purpose of this study was to determine the past-year prevalence estimates of cigarette smoking and eligibility for low-dose computed tomography (LDCT) lung cancer screening among older U.S. adults and examine potential variations in these estimates by sexual orientation. Data were from the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) and included in-person interviews with a nationally representative sample of non-institutionalized adults aged 18 and older. Eligibility for LDCT was based on U.S. Centers for Medicare and Medicaid Services (CMS) guidelines. Analyses included participants aged 55–77 (n?=?9,635). Overall, 17.5% of older adult respondents reported past-year smoking. Overall rates of past-year cigarette smoking were influenced by sex and sexual orientation with males reporting higher rates compared to females. Among both males and females, smoking was most prevalent among bisexual individuals. Eligibility for LDCT was also higher among males compared to females and among bisexually identified adults relative to homosexual and heterosexual-identified adults. Overall, 11.2% of older U.S. adults met eligibility for LDCT lung cancer screening. Eligibility for LDCT lung screening is associated with sexual orientation; the highest rates of eligibility are among bisexual women and men (26.9 and 24.5%, respectively). The current study found variations in cigarette smoking and eligibility for LDCT lung cancer screening (a proxy for chronic high-risk smoking) among older U.S. adults based on sexual orientation. Efforts to increase screening should take into account these differences.     

Cancer screening practices of adult survivors of retinoblastoma at risk of second cancers

BACKGROUND: The aim of the current study was to investigate the pattern of cancer screening behavior in adult retinoblastoma survivors, who are at high risk of developing second cancers. METHODS: Self-reported cancer screening practices were investigated in a cohort of retinoblastoma survivors to evaluate whether they were receiving adequate screening for specific cancers and compare these rates with those of other adult survivors of childhood cancer and the general population. The prevalence of breast self-examination, clinical breast examination, mammography, Papanicolaou (Pap) test, testicular self-examination, and magnetic resonance imaging (MRI) or computed tomography (CT) scanning was determined from computer-aided telephone interviews with 836 retinoblastoma survivors aged >18 years. RESULTS: Among female survivors, 87% had a Pap test within the past 2 years, and 76% of females age >40 years reported having a mammogram within the past 2 years; 17.4% of male survivors had performed monthly testicular self-examinations. A significantly higher proportion of hereditary compared with nonhereditary survivors reported having undergone an MRI or CT scan in the past 5 years. Higher education, greater contact with the medical care system, and having a second cancer were found to be associated positively with most screening practices. Cancer screening practices reported by retinoblastoma survivors were similar to national screening rates for breast, cervical, and testicular cancer. CONCLUSIONS: To the authors' knowledge, the current study provides the first report of cancer screening practices of retinoblastoma survivors. Survivors of hereditary retinoblastoma should be encouraged to maintain, if not increase, their current screening practices to ensure early detection of second cancers in this high-risk population.     

Adult Life after Childhood Cancer in Scandinavia: Diabetes mellitus following treatment for cancer in childhood

AimAn increased risk for diabetes mellitus (DM) adds significantly to the burden of late complications in childhood cancer survivors. Complications of DM may be prevented by using appropriate screening. It is, therefore, important to better characterise the reported increased risk for DM in a large population-based setting.Materials and methodsFrom the national cancer registries of the five Nordic countries, a cohort of 32,903 1-year survivors of cancer diagnosed before the age of 20 between start of cancer registration in the 1940s and 1950s through 2008 was identified; 212,393 comparison subjects of the same age, gender and country were selected from national population registers. Study subjects were linked to the national hospital registers. Absolute excess risks (AERs) and standardised hospitalisation rate ratios (SHRRs) were calculated.ResultsDM was diagnosed in 496 childhood cancer survivors, yielding an overall SHRR of 1.6 (95% confidence interval (CI), 1.5–1.8) and an AER of 43 per 100,000 person-years, increasing from approximately 20 extra cases of DM in ages 0–19 to more than 100 extra cases per 100,000 person-years in ages ⩾50. The relative risks for DM were significantly increased after Wilms’ tumour (SHRR, 2.9), leukaemia (2.0), CNS neoplasms (1.8), germ-cell neoplasms (1.7), malignant bone tumours (1.7) and Hodgkin’s lymphoma (1.6). The risk for DM type 2 was slightly higher than that for type 1.ConclusionChildhood cancer survivors are at increased risk for DM, with absolute risks increasing throughout life. These findings underscore the need for preventive interventions and prolonged follow-up of childhood cancer survivors.     

Health behaviors of cancer survivors: data from an Australian population-based survey

Objective With increases in cancer survival, promotion of healthy lifestyle behaviors among survivors is receiving considerable attention. This study compared health behaviors among a large sample of Australian adult cancer survivors with an age- and sex-matched cohort of people with no cancer history. Methods Using the Australian National Health Survey, 968 cancer survivors were identified, and randomly matched by age and sex to 5,808 respondents without a history of cancer. Six health behaviors were compared (smoking, physical activity, servings of vegetables, servings of fruit, alcohol use, skin checks), along with overweight and obesity, using polytomous logistic regression analyses controlling for selected chronic conditions. Models were applied across both groups and by tumor site. Results Compared to the non-cancer comparison group, cancer survivors were significantly more likely to be current (OR = 1.35) smokers, particularly those under 40 years (OR = 1.69), and more likely to have regular skin checks (OR = 1.76). Although not significant, there was consistent evidence that cancer survivors were slightly more likely to be overweight or obese (p = 0.065) and have higher levels of alcohol consumption (p = 0.088). There was no evidence of differences between survivors and controls for levels of physical inactivity, vegetable consumption or fruit consumption. Women with a history of gynecological cancers were much more likely to be current smokers (OR = 2.37), while other differences by sex and cancer site were consistent with overall patterns. Cancer survivors were also significantly more likely to report having a range of co-morbid chronic medical conditions. Conclusion Given their increased risk of second cancers and co-morbid chronic conditions, the lack of difference in behavioral risk factors confirms the need for a focus on improving the health behaviors of cancer survivors. Collaborative chronic disease management models may be particularly appropriate in this regard.     

Thyroid cancer and multiple primary tumors in the SEER cancer registries

Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program (1973-2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35-50%; excess absolute risk (EAR) = 0.38/10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06-1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects.     

Radiation-induced cancers following radiotherapy

Improved radiotherapy for cancer has produced a large population of long-term survivors. These survivors, however, appear to have a greater risk of second primary cancers than would be expected based on the incidence of first primary cancers in the general population. The etiology of radiation-induced cancer is multifactorial and incompletely understood, and there is no firm diagnostic criteria for radiation-induced cancer because there are no specific histopathological findings. The incidence of radiation-induced cancers following radiotherapy was estimated to be about 0.3% in 5-year survivors, based on mail surveys (in 1979 & 1984) in Japan. It seems that the benefit of treatment outweighs the risk of developing secondary tumors. However, we should avoid excess treatment of patients with Hodgkin's disease or many pediatric malignancies who will be able to survive a long time after treatment. The relative carcinogenicity of various combinations of radiation and chemotherapeutic agents is now being established. Chemoradiotherapy is now frequently used for treatment of various malignancies which are considered to be uncontrollable by chemotherapy or radiotherapy alone. We should minimize their carcinogenic effects and the risk of developing secondary treatment-related tumors, to produce an optimal therapeutic gain. Long-term close follow-up is necessary for these patients.     

Second primary malignancies among patients with soft tissue tumors in Sweden

Survival from soft tissue tumors (STTs) has been improved because of the successful treatment. One of the late sequelae in STT survivors is the development of a second malignancy. The present study aimed at quantifying risks for second malignancies in patients with STTs, and risks for second STTs after other primary malignancies. Adjusted standardized incidence ratios (SIRs), calculated from the Swedish Family-Cancer Database, were used as a measure of risk. Among 6,671 primary STT patients, a total of 650 second malignancies occurred. Besides second STTs, other cancer sites with an increased SIR were the nervous system, endocrine glands, skin (melanoma and squamous cell carcinoma) and prostate; the risk for non-Hodgkin lymphoma (NHL) was also increased. The overall risk of second malignancies decreased in the following order: fibrosarocma (1.63) > myxosarcoma (1.48) > leiomyosarcoma (1.44) > liposarcoma (1.21). An increased risk of second STTs after primary cancers of the bone, ovary, nervous system, cervix, thyroid gland, skin, endometrium, breast, upper aerodigestive tract, and after Hodgkin disease, NHL and leukemia was also noted. This study showed that the incidence of second primary malignancies in patients with STTs was increased, but the SIRs varied among specific cancer sites. Besides therapeutic effects, the associations between STTs and bone and nervous system tumors suggested that cancer syndromes, such as neurofibromatosis type 1 and Li-Fraumeni syndrome, may partly explain the excesses. The associations of STTs with cancers of the skin (squamous cell carcinoma and melanoma) and with NHL may be related to immunodeficiency.     

Disparities in Cancer Care and the Asian American Population

Asian Americans are the only racial/ethnic group in the U.S. for whom cancer is the leading cause of death in men and women, unlike heart disease for all other groups. Asian Americans face a confluence of cancer risks, with high rates of cancers endemic to their countries of origin due to infectious and cultural reasons, as well as increasing rates of “Western” cancers that are due in part to assimilation to the American diet and lifestyle. Despite the clear mortality risk, Asian Americans are screened for cancers at lower rates than the majority of Americans. Solutions to eliminate the disparity in cancer care are complicated by language and cultural concerns of this very heterogeneous group. This review addresses the disparities in cancer screening, the historical causes, the potential contribution of racism, the importance of cultural perceptions of health care, and potential strategies to address a very complicated problem. Noting that the health care disparities faced by Asian Americans may be less conspicuous than the structural racism that has inflicted significant damage to the health of Black Americans over more than four centuries, this review is meant to raise awareness and to compel the medical establishment to recognize the urgent need to eliminate health disparities for all.Implications for PracticeCancer is the leading cause of death in Asian Americans, who face cancers endemic to their native countries, perhaps because of infectious and cultural factors, as well as those faced by all Americans, perhaps because of “Westernization” in terms of diet and lifestyle. Despite the mortality rates, Asian Americans have less cancer screening than other Americans. This review highlights the need to educate Asian Americans to improve cancer literacy and health care providers to understand the important cancer risks of the fastest‐growing racial/ethnic group in the U.S. Eliminating disparities is critical to achieving an equitable society for all Americans.     

Frailty in childhood cancer survivors

Young adult childhood cancer survivors are at an increased risk of frailty, a physiologic phenotype typically found among older adults. This phenotype is associated with new‐onset chronic health conditions and mortality among both older adults and childhood cancer survivors. Mounting evidence suggests that poor fitness, muscular weakness, and cognitive decline are common among adults treated for childhood malignancies, and that risk factors for these outcomes are not limited to those treated with cranial radiation. Although the pathobiology of this phenotype is not known, early cellular senescence, sterile inflammation, and mitochondrial dysfunction in response to initial cancer or treatment‐related insults are hypothesized to play a role. To the authors' knowledge, interventions to prevent or remediate frailty among childhood cancer survivors have not been tested to date. Pharmaceutical, nutraceutical, and lifestyle interventions have demonstrated some promise. Cancer 2015;121:1540–1547 . © 2014 American Cancer Society.     

Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment.

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin's disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin's disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3. 3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55. 9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy). CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin's disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin's disease require detailed investigation.     

Skin cancer and non-Hodgkin's lymphoma as second malignancies. markers of impaired immune function?

Successes in cancer therapy have led to increasing numbers of cancer survivors, who are at risk of developing second primary cancers. Therapy- or disease-induced suppression of the immune function may predispose cancer patients to a second malignancy. An excess of squamous cell skin cancers (SCC) and non-Hodgkin's lymphomas has been found in immunosuppressed patients. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals to calculate the risk of second primary skin cancers and non-Hodgkin's lymphomas following a previous malignancy. A total of 4301 second skin cancers and 1672 non-Hodgkin's lymphomas were identified. Standardised incidence ratios (SIR)s and 95% Confidence Intervals (CIs) were calculated and compared. Among 14 different sites for male or female first primary malignancies, 11 of these sites were followed by an increased risk of skin cancer (SIRs for males for risk of skin cancer as a second primary cancer: 14.1 for SCC; 9.7 for melanoma; 6.1 for leukaemia as the first site; SIRs for females for risk of skin cancer: 14.6 for SCC; 6.8 for larynx; 6.2 for upper aerodigestive tract (UADT) as the first site). The risk of non-Hodgkin's lymphoma was increased after 10 of 14 different male neoplasms and 12 of 17 different female neoplasms. (SIRs for males for risk of non-Hodgkin's lymphoma as a second primary cancer: 6.4 for non-Hodgkin's lymphoma; 3.2 for leukaemias; 3.1 for multiple myeloma as the first site; SIRs for females for risk of non-Hodgkin's lymphoma as a second primary cancer: 12.5 for leukaemias; 7.0 for Hodgkin's disease; 3.6 for UADT as the first site). The high, and after certain sites, very high risks of second skin cancer and non-Hodgkin's lymphoma suggest that immune suppression may be a contributory mechanism.