Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study

BACKGROUND: Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group. METHODS: As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1,607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS. RESULTS: One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (>/= 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1-694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% CI 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7-109.8), blood clots (RR = 5.7; 95% CI 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy. CONCLUSIONS: Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy.     

The cancer screening practices of adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

BACKGROUND: The current study characterized the self-reported cancer screening practices of adult survivors of childhood cancer. METHODS: A cohort of 9434 long-term survivors of childhood cancer and a comparison group of 2667 siblings completed a 289-item survey that included items regarding cancer-screening practices. RESULTS: Overall, 27.3% of female respondents reported performing breast self-examination (BSE) regularly, 78.2% reported undergoing a Papanicolaou smear within the previous 3 years, 62.4% underwent a clinical breast examination (CBE) within the last year, and 20.9% had gotten a mammogram at least once in their lifetime. Approximately 17.4% of male respondents reported performing regular testicular self-examination (TSE). Women age > or =30 years who had been exposed to chest or mantle radiation therapy were more likely to report undergoing CBE (odds ratio [OR], 1.59; 95% confidence interval [95% CI], 1.32-1.92) and mammography (OR, 1.92; 95% CI, 1.47-2.56). Compared with the sibling comparison group, survivors demonstrated an increased likelihood of performing TSE (OR, 1.52; 95% CI, 1.22-1.85) or BSE (OR, 1.30; 95% CI, 1.10-1.52), of having undergone a CBE within the last year (OR, 1.18; 95% CI, 1.02-1.35), and of ever having undergone a mammogram (OR, 1.82; 95% CI, 1.52-2.17). CONCLUSIONS: The results of the current study demonstrate that the cancer screening practices among survivors of childhood cancer are below optimal levels. Primary care physicians who include childhood cancer survivors among their patients could benefit these individuals by informing them about future cancer risks and recommending appropriate evidence-based screening.     

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Twenty years of follow-up among survivors of childhood and young adult acute myeloid leukemia: a report from the Childhood Cancer Survivor Study

BACKGROUND: Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML). METHODS: This analysis included 272 5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age < or =21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed. RESULTS: The average follow-up was 20.5 years (range, 5-33 years). The overall survival rate was 97% at 10 years (95% confidence interval [95%CI], 94%-98%) and 94% at 20 years (95% CI, 90%-96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%-9.6%) and 8.6% at 20 years (95% CI, 5.1%-12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%-3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%-7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8%; P < .001). Among those aged > or =25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67%; P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively; P < .01). Employment rates were similar between survivors, siblings, and the general population (93%, 97.6%, and 95.8%, respectively). CONCLUSIONS: Long-term survival from childhood AML > or =5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the individual family unit, although it was not different from the general United States population.     

A prospective study of periodontal disease and pancreatic cancer in US male health professionals

Two previous cohort studies reported positive associations between tooth loss or periodontitis and pancreatic cancer risk. Data on periodontal disease were obtained at baseline and every other year thereafter in a cohort of 51,529 male health professionals aged 40-75 years. A total of 216 patients were diagnosed with incident pancreatic cancer during 16 years of follow-up. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models controlling for potential confounders, including detailed smoking history. All statistical tests were two-sided. Compared with no periodontal disease, history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline number of natural teeth and cumulative tooth loss during follow-up were not strongly associated with pancreatic cancer. The association between periodontal disease and increased risk of pancreatic cancer may occur through plausible biologic mechanisms, but confirmation of this association is necessary.     

Probability of parenthood after early onset cancer: a population-based study

We evaluated in a population-based setting the postdiagnosis parenthood among survivors compared with the fertility patterns of siblings. Cancer patients aged 0-34 years at diagnosis were identified from the Finnish Cancer Registry (N = 25,784), and their siblings (N = 44,611) by registry linkage. Further linkage identified the offspring of the patient and sibling cohorts. The relative probabilities of parenthood for first and second births separately were estimated for male and female survivors in different diagnostic age-groups and subsites using a Cox proportional hazards model, with age as the time variable and adjusting for the birth cohort of parents. In addition, estimates were calculated for 5 diagnostic eras in all subsites combined. Compared to siblings, both female and male cancer survivors were less likely to parent at least 1 child (RR 0.46, 95% CI 0.44-0.48 and RR 0.57, 95% CI 0.54-0.60, respectively). The relative probability of parenthood was especially low in male childhood cancer survivors and female young adult cancer survivors. However, cancer patients were only slightly less likely than siblings to parent a second child, with RR 0.91, 95% CI 0.86-0.97 and RR 0.95, 95% CI 0.89-1.01 for females and males, respectively. The relative probability of parenthood increased over calendar time among young adult cancer patients. The relative probability of parenthood following early onset cancer was overall significantly reduced by approximately 50%. Parenting a second child, however, was not reduced among pediatric and adolescent survivors, and only slightly reduced among early adulthood cancer survivors compared to siblings.     

Psychological outcomes of siblings of cancer survivors: a report from the Childhood Cancer Survivor Study

Objective: To identify risk factors for adverse psychological outcomes among adult siblings of long‐term survivors of childhood cancer. Methods: Cross‐sectional, self‐report data from 3083 adult siblings (mean age 29 years, range 18–56 years) of 5 + year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory‐18 (BSI‐18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors, were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression. Results: Self‐reported symptoms of psychological distress, as measured by the global severity index of the BSI‐18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI‐18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42–3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18–3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05–3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08–4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05–3.98). Conclusions: These findings suggest that siblings of long‐term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long‐term psychological impairment who may benefit from preventive risk‐reduction strategies during childhood while their sibling with cancer is undergoing treatment. Copyright © 2010 John Wiley & Sons, Ltd.     

Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study

Purpose

The purpose of this study was to assess the prevalence of male infertility and treatment-related risk factors in childhood cancer survivors.

Methods

Within the Childhood Cancer Survivor Study, 1,622 survivors and 274 siblings completed the Male Health Questionnaire. The analysis was restricted to survivors (938/1,622; 57.8 %) and siblings (174/274; 63.5 %) who tried to become pregnant. Relative risks (RR) and 95 % confidence intervals (CI) for the prevalence of self-reported infertility were calculated using generalized linear models for demographic variables and treatment-related factors to account for correlation among survivors and siblings of the same family. All statistical tests were two-sided.

Results

Among those who provided self-report data, the prevalence of infertility was 46.0 % in survivors versus 17.5 % in siblings (RR?=?2.64, 95 % CI 1.88–3.70, p?<?0.001). Of survivors who met the definition for infertility, 37 % had reported at least one pregnancy with a female partner that resulted in a live birth. In a multivariable analysis, risk factors for infertility included an alkylating agent dose (AAD) score ≥3 (RR?=?2.13, 95 % CI 1.69–2.68 for AAD ≥3 versus AAD <3), surgical excision of any organ of the genital tract (RR?=?1.63, 95 % CI 1.20–2.21), testicular radiation ≥4 Gy (RR?=?1.99, 95 % CI 1.52–2.61), and exposure to bleomycin (RR?=?1.55, 95 % CI 1.20–2.01).

Conclusion

Many survivors who experience infertility father their own children, suggesting episodes of both fertility and infertility. This and the novel association of infertility with bleomycin warrant further investigation.

Implications for Cancer Survivors

Though infertility is common, male survivors reporting infertility often father their own children. Bleomycin may pose some fertility risk.     

Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

PURPOSE: To determine whether adult survivors (>or= 18 years of age) of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity and to assess patient and treatment variables that influence risk. PATIENTS AND METHODS: A retrospective cohort of participants of the Childhood Cancer Survivor Study was used to compare 1,765 adult survivors of childhood ALL to 2,565 adult siblings of childhood cancer survivors. Body-mass index (BMI; kilograms per square meter), calculated from self-reported heights and weights, was used to determine the prevalence of being overweight (BMI, 25-29.9) or obese (BMI >or= 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors relative to the sibling control group. RESULTS: The age- and race-adjusted OR for being obese in survivors treated with cranial radiation doses >or= 20 Gy in comparison with siblings was 2.59 for females (95% CI, 1.88 to 3.55; P <.001) and 1.86 for males (95% CI, 1.33 to 2.57; P <.001). The OR for obesity was greatest among females diagnosed at 0 to 4 years of age and treated with radiation doses >or= 20 Gy (OR, 3.81; 95% CI, 2.34 to 5.99; P <.001). Obesity was not associated with treatment consisting of chemotherapy only or with cranial radiation doses of 10 to 19 Gy. CONCLUSION: Cranial radiotherapy >or= 20 Gy is associated with an increased prevalence of obesity, especially in females treated at a young age. It is imperative that healthcare professionals recognize this risk and develop strategies to enhance weight control and encourage longitudinal follow-up.     

Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population‐based cohort study

Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer‐directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population‐based cohort study included all 1‐year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow‐up in the hospital registries were 10 years (range: 0–42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6–1.7], which corresponds to an absolute excess of 360 (95% CI: 330–390) hospitalizations per 100,000 person‐years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2–20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0–4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects.     

Pulmonary complications in survivors of childhood and adolescent cancer. A report from the Childhood Cancer Survivor Study

BACKGROUND: The Childhood Cancer Survivor Study is a resource that was designed to investigate long-term effects among 5-year survivors of childhood and adolescent malignancies. Previous studies have shown that exposure to chemotherapy and/or radiation can compromise pulmonary function in these survivors of childhood cancer. METHODS: Using information obtained from questionnaires from 12,390 childhood cancer survivors and 3546 randomly selected siblings, the authors evaluated the rate of first occurrence of 15 selected pulmonary conditions in three periods: during therapy, from the end of therapy to 5 years postdiagnosis, and >/= 5 years postdiagnosis. Multivariate analyses were used to determine the relative risks with 95% confidence intervals of reported pulmonary conditions by exposure to the following treatment variables: radiation therapy to the chest, bleomycin, cyclophosphamide, busulfan, lomustine (CCNU), and/or carmustine (BCNU). RESULTS: Compared with siblings, survivors had a statistically significant increased relative risk (RR) of lung fibrosis, recurrent pneumonia, chronic cough, pleurisy, use of supplemental oxygen, abnormal chest wall, exercise-induced shortness of breath, bronchitis, recurrent sinus infection, and tonsillitis for all three periods. During the period of >or= 5 years postdiagnosis, statistically significant associations were present for lung fibrosis and chest radiation (RR, 4.3; P = 0 001); for supplemental oxygen use and chest radiation (RR, 1.8; P < 0.001), BCNU (RR, 1.4; P = 0.05), bleomycin (RR, 1.7; P = 0.001), busulfan (RR, 3.2; P = 0.002), CCNU (RR, 2.1; P < 0.001), and cyclophosphamide (RR, 1.5; P = 0.01); for recurrent pneumonia and chest radiation (RR, 2.2; P = 0.001) and cyclophosphamide (RR, 1.6; P = 0.04); for chronic cough and chest radiation (RR, 2.0; P < 0.001), bleomycin (RR, 1.9; P < 0.001), and cyclophosphamide (RR, 1.3; P = 0.004); and for pleurisy and chest radiation (RR, 1.4; P = 0.02) and busulfan (RR, 5.1; P = 0.02). Chest radiation was associated with a 3.5% cumulative incidence of lung fibrosis at 20 years after diagnosis. CONCLUSIONS: For self-report of pulmonary conditions, treatment-related factors that continue to manifest > 5 years after diagnosis and treatment are important determinants of risk. Continued follow-up of childhood cancer survivors is needed to evaluate the impact of pulmonary conditions on quality of life.     

Male breast cancer incidence among atomic bomb survivors

To learn more about the role of ionizing radiation in the development of male breast cancer, we evaluated male breast cancer incidence among 45 880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Male breast cancers, diagnosed between January 1, 1958, and December 31, 1998, were identified through the Hiroshima and Nagasaki Tumor Registries. Nine male breast cancers were diagnosed among exposed Life Span Study members (crude rate = 1.8 per 100,000 person-years), and three were diagnosed among nonexposed cohort members (crude rate = 0.5 per 100,000 person-years). A statistically significant dose-response relation was observed (excess relative risk per sievert = 8, 95% confidence interval = 0.8 to 48; P = .01). Our finding of a statistically significant association between ionizing radiation and male breast cancer incidence adds to the very limited information that shows an association between radiation exposure and an increased risk of male breast cancer.     

Long-term risk of renal and urinary tract diseases in childhood cancer survivors: A population-based cohort study

BackgroundChildhood cancer has been associated with long-term risk of urinary tract diseases, but risk patterns remain to be comprehensively investigated. We analysed the lifetime risk of urinary tract diseases in survivors of childhood cancer in the Nordic countries.MethodsWe identified 32,519 one-year survivors of childhood cancer diagnosed since the 1940s and 1950s in the five Nordic cancer registries and selected 211,156 population comparisons of a corresponding age, sex, and country of residence from the national population registries. To obtain information on all first-time hospitalizations for a urinary tract disease, we linked all study subjects to the national hospital registry of each country. Relative risks (RRs) and absolute excess risks (AERs) and associated 95% confidence intervals (CIs) for urinary tract diseases among cancer survivors were calculated with the appropriate morbidity rates among comparisons as reference.ResultsWe observed 1645 childhood cancer survivors ever hospitalized for urinary tract disease yielding an RR of 2.5 (95% CI 2.4–2.7) and an AER of 229 (95% CI 210–248) per 100,000 person-years. The cumulative risk at age 60 was 22% in cancer survivors and 10% in comparisons. Infections of the urinary system and chronic kidney disease showed the highest excess risks, whereas survivors of neuroblastoma, hepatic and renal tumours experienced the highest RRs.ConclusionSurvivors of childhood cancer had an excess risk of urinary tract diseases and for most diseases the risk remained elevated throughout life. The highest risks occurred following therapy of childhood abdominal tumours.     

Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age

Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explored the temporal patterns of this disease among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program. We identified 22,759 patients from January 1, 1975, through December 31, 2004, with esophageal cancer, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Among white men, increases in the incidence of esophageal cancer were largely attributed to a 463% increase in the incidence of adenocarcinoma over this time period, from 1.01 per 100,000 person-years (95% confidence interval [CI] = 0.90 to 1.13) in 1975-1979 to 5.69 per 100,000 person-years (95% CI = 5.47 to 5.91) in 2000-2004. A similar rapid increase was also apparent among white women, among whom the adenocarcinoma rate increased 335%, from 0.17 (95% CI = 0.13 to 0.21) to 0.74 per 100,000 person-years (95% CI = 0.67 to 0.81), over the same time period. Adenocarcinoma rates rose among white men and women in all stage and age groups, indicating that these increases are real and not an artifact of surveillance.     

Trends in childhood acute lymphoblastic leukemia in Western Australia, 1960-2006

Increases in the incidence of childhood acute lymphoblastic leukemia (ALL) have been reported in some countries, while other reports from similar geographical regions have indicated stable rates. The reasons for the discrepancies have been debated in the literature, with the focus on whether the observed increases are "real" or an artifact resulting from improvements in diagnosis, case ascertainment and population coverage over time. We used population-based data from Western Australia to investigate trends in the incidence of childhood ALL between 1960 and 2006. Age-standardized incidence rates (ASRs) and rate ratios (indicating annual percent change) were estimated using Poisson regression. Between 1960 and 2006, the ASR was 3.7 per 100,000 person-years, with an annual percent increase of 0.40% (95% CI: -0.20, 1.00). Between 1982 and 2006, the ASR was 3.8, with an annual percent increase of 0.80% (95% CI = -0.70 to 2.30). This increased to 1.42% (95% CI: -0.30, 3.0) when a sensitivity analysis was undertaken to assess the effect of excluding the final 2 years of data. Annual increases of 3.7% (95% CI: -0.50, 8.00) among children aged 5-14 years, and of 3.10% (95% CI: 0.50, 5.70) in girls, were observed for this latter period. These results were supported by national Australian incidence data available for 1982-2003. There may have been a small increase in the incidence of ALL since 1982 among girls and older children, but an overall increase appears unlikely. No impact of folate supplementation or fortification is apparent.     

Visual, auditory, sensory, and motor impairments in long-term survivors of hematopoietic stem cell transplantation performed in childhood: results from the Bone Marrow Transplant Survivor study

BACKGROUND: Because of treatment-related toxicity, research is increasingly being focused on long-term sequelae secondary to hematopoietic stem cell transplantation (HSCT) in survivor populations. METHODS: This study describes the incidence of auditory, sensory, motor, and visual impairments, including cataracts, among 235 individuals who were treated with HSCT during childhood or adolescence. Outcomes were compared with 705 siblings of childhood cancer survivors. Participants completed a survey with questions on posttransplant organ system impairments. Approximately half of survivors were transplanted when younger than 10 years of age. The median length of followup was 11 years. RESULTS: The cumulative incidence of cataracts was 36% at 15 years post-HSCT, although cataracts occurred only in those who received total body irradiation as an HSCT conditioning agent or head irradiation before transplant. Persistent pain was reported by 21% of survivors. Loss of hearing in one or both ears, and legal blindness in one or both eyes, each occurred after transplant in 2% of survivors. Occurrences were uncommon, but survivors were 4.3 times (95% confidence interval [CI]: 2.0-9.4) more likely to report coordination problems, 7.7 times (95% CI: 3.2-18.5) more likely to report chewing or swallowing problems, and 3.5 times (3.5; 95% CI: 1.6-7.9) more likely to report muscle weakness than those in the comparison group. Muscle weakness was strongly associated with positive history of chronic graft-versus-host disease. CONCLUSIONS: Increased risks were found for motor impairments, hearing loss, vision loss, and persistent pain among study participants. Cataracts were a frequent adverse effect, suggesting that close monitoring with appropriate intervention for preservation of vision, particularly among those who received total body irradiation, should be a primary goal in survivors of HSCT performed in childhood.     

Long-term risk of colorectal cancer after screen-detected adenoma: Experiences from a Danish gFOBT-positive screening cohort

Fecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all FOBT-positive persons have screen-detected adenomas. Despite removal of these, patients with large/multiple adenomas have increased risk of later developing new advanced adenomas and CRC. International guidelines exist for colonoscopic surveillance following adenoma removal. These divide patients into low-, intermediate- and high-risk groups. We followed 711 FOBT-positive patients with screening adenoma identified during population-based CRC screening in two Danish counties in 2005–2006. As reference population, we included 1,240,348 persons in the same age group from the rest of Denmark not included in the screening. We estimated the long-term CRC risk stratified by adenoma findings during screening and compared to the reference group. After 12 years follow-up, the CRC incidence among all adenoma patients was 322 cases per 100,000 person-years (95% confidence interval [CI]: 212–489) ranging from 251 (95% CI: 94–671) to 542 (95% CI: 300–978) cases per 100,000 person-years in the low- and high-risk groups, respectively. In the reference population, the CRC incidence was 244 (95% CI: 242–247) per 100,000. Patients with screen-detected high-risk adenomas after a positive FOBT had an almost doubled risk of CRC compared to the reference population (adjusted hazard ratio [aHR] 1.95, 95% CI: 1.08–3.51), and the incidence in those with no follow-up visits was over 3.6 (aHR 3.64, 95% CI: 1.82–7.29) times the incidence in the reference population. The increased CRC risk could be controlled if high-risk patients underwent follow-up colonoscopy (aHR 0.87, 95% CI: 0.28–2.69).     

Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study

Chemotherapy and radiation therapy may increase risk for interstitial pneumonitis (IP) in breast cancer patients, but there are little current population-based data on IP incidence in these patients. We assessed population-based incidence rates (IRs) of IP among Danish breast cancer patients and compared these with IRs for the Danish general population. Through the Danish Cancer Registry, we identified all Danish breast cancer patients (n=35 823) diagnosed between 1994 and 2004. Treatment data were obtained from the Danish Breast Cancer Cooperation Group database, and data on IP, from the Danish National Registry of Patients. We computed IRs of IP among breast cancer patients and age-standardised incidence rate ratios (SIRs) comparing breast cancer patients with the general population. During follow-up, 28 breast cancer patients were registered with an IP diagnosis (IR=17.3 per 100,000 person-years (p-y) (95% confidence intervals (95% CI): 11.7-24.6)). When follow-up was restricted to 1 year after the first breast cancer diagnosis, eight patients with IP were identified (IR=23.4 per 100,000 p-y (95% CI: 11.0-44.1)). The SIR comparing breast cancer patients with the general population was 8.4 (95% CI: 5.7-11.9). Thus, although IP is a rare adverse event among breast cancer patients, its risk is substantially higher than that in the general population.     

Time Trend Analysis of Oral Cancer in Iran from 2005 to 2010

Background: There is a considerable lack of understanding of oral cancer incidence, especially its time trend in Iran. In this study, the authors aimed to analyze time trend of oral cancer incidence with a focus on differences by gender in a period of six years - from 2005 to 2010. Materials and Methods: Both population-based cancer registry and national cancer registry (NCR) data based on pathologic reports from 2005 to 2010 were obtained from the Ministry of Health and Medical Education (MOHME). Population data were also received from Statistical Centre of Iran. Age-standardized incidence rates (ASRs) based on the World Standard Population were then calculated. Finally, Negative Binomial regression was run for time trend analysis. Results: The maximum ASR for males was calculated as 2.5 per 100,000 person-years in 2008 and the minimum was observed as 1.9 per 100,000 person-years in 2005 and 2006. Meanwhile, the maximum ASR for females was estimated as 1.8 per 100,000 person-years in 2009 and the minimum was calculated as 1.6 per 100,000 person-years in 2005 and 2006. Additionally, in females, incidence risk ratio (IRR) did not show a clear decreasing or increasing trend during the six years. Nevertheless, in males an increasing trend was observed. The maximum IRR adjusted for age group and province, for females was reported in 2009 (IRR=1.05 95% CI: 0.90-1.23), and for males was estimated in 2010 (IRR=1/2 95% CI: 1.04 - 1.38). Conclusions: Our findings highlight disparities between oral cancer incidence trends in males and females over the six years from 2005 to 2010.