Highest Standardized Incidence Ratios Research Articles

Multiple primary malignancies for squamous cell carcinoma and adenocarcinoma of the esophagus.

Patients with esophageal cancer (EC) frequently have multiple primary cancers. We conducted the present study to assess the risk of multiple primary malignancies for patients with squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus and to investigate the influence of multiple primary tumors on the prognosis of EC patients. Using the data of 44,091 EC patients from the Surveillance Epidemiology and End Results (SEER) database, we calculated the standardized incidence ratios (SIRs) for overall multiple primary cancers and cancers at particular sites among EC survivors. The SIRs of esophageal SCC and AC patients were compared using Poisson regression. The Kaplan-Meier (KM) method was used for survival analysis. Multiple primary cancer risk was significantly increased among both esophageal SCC and AC survivors (SIR: 2.28 and 1.57, respectively; P<0.001). Among SCC patients, the highest SIRs were found in the oral cavity and pharynx (SIR: 16.54), esophagus (SIR: 10.02), and larynx (SIR: 10.34). Also, the highest SIRs following AC cases were observed in the esophagus (SIR: 8.81), stomach (SIR: 9.29), and small intestine (SIR: 4.95). SIRs for the oral cavity and pharynx, lung, and larynx were significantly higher among SCC survivors than AC survivors (all P<0.05). KM analysis revealed no significant difference of overall survival (OS) for multiple primary cancers, including those of the esophagus, stomach, oral cavity and pharynx, and lung among EC patients (log rank =2.04; P=0.564), except for prostate cancer (log rank =96.65; P<0.001). Multiple primary malignancy risk differed by the histological type of esophageal SSC and AC survivor. However, no significant relationship between survival and the multiple primary cancer sites, except for prostate cancer, was observed.

Spectrum of malignancies among the population of adults living with HIV infection in China: A nationwide follow-up study, 2008-2011.

BackgroundAlthough increasingly studied in high-income countries, there is a paucity of data from the Chinese population on the patterns of cancer among people living with HIV (PLHIV).MethodsWe conducted a nationwide follow-up study using routinely collected data for adult PLHIV diagnosed on or before 31 December 2011 and alive and in care as of 1 January 2008. Participants were observed from 1 January 2008 (study start) to 30 June 2012 (study end). Main outcome measures were gender-stratified age-standardized incidence rates for China (ASIRC) and standardized incidence ratios (SIR) for all malignancy types/sites observed.ResultsAmong 399,451 subjects, a majority was aged 30–44 years (49.3%), male (69.8%), and Han Chinese (67.9%). A total of 3,819 reports of cancer were identified. Overall, ASIRC was 776.4 per 100,000 for males and 486.5 per 100,000 for females. Malignancy sites/types with highest ASIRC among males were lung (226.0 per 100,000), liver (145.7 per 100,000), and lymphoma (63.1 per 100,000), and among females were lung (66.8 per 100,000), lymphoma (48.0 per 100,000), stomach (47.8 per 100,000), and cervix (47.6 per 100,000). Overall SIR for males was 3.4 and for females was 2.6. Highest SIR was observed for Kaposi sarcoma (2,639.8 for males, 1,593.5 for females) and lymphoma (13.9 for males, 16.0 for females).ConclusionsThese results provide evidence of substantial AIDS-defining and non-AIDS-defining cancer burden among adult Chinese PLHIV between 2008 and 2011. Although further study is warranted, China should take action to improve cancer screening, diagnosis, and treatment for this vulnerable population.

The Pattern of Non-AIDS-defining Cancers in the HIV Population: Epidemiology, Risk Factors and Prognosis. A Review.

The advent of highly active antiretroviral therapy (HAART) has significantly reduced the incidence of AIDS events, including AIDS-defining malignancies. Nevertheless, several cohort studies conducted in the post-HAART period have reported an increasing risk of non-AIDS-defining cancers (NADC). Overall, the potential mechanisms leading to an increased risk of developing NADCs probably involve multiple known and unknown factors. In addition to ageing, chronic inflammation and ongoing immune system dysregulation, other contributing factors are co-infection with potentially oncogenic viruses (HBV, HCV, HPV, EBV) and high-risk behaviours such as tobacco smoking. As a consequence of these risk factors, high standardized incidence ratios have been consistently reported, mainly in cohort studies regarding smoking-related cancers (lung cancer, but also pharyngeal and kidney cancer), due to the far more common cigarette smoking habit in the HIV-population. Also in the setting of infection-related malignancies, the high frequency of liver cancer, as a consequence of HBV and HCV co-infection is well known. Similarly, HPV infection accounts for the higher risk of anal cancer. On the same line, Hodgkin lymphoma is more frequent in the HIV population, due to the dysregulation and proliferation of EBV-infected lymphocytes. Several studies addressed the direct relationship between immunosuppression and cancer progression, showing that subjects with HIV infection experience higher cancer-specific mortality, as compared to the general population, independently of cancer stage or cancer treatment. In the HIV population, for many NADCs, the prognosis is still worse as compared to the general population. However, an improvement has been reported over the last decades, mainly thanks to more available and adequate treatment chances.

Total body irradiation dose and risk of subsequent neoplasms following allogeneic hematopoietic cell transplantation

AbstractWe examined the impact of total body irradiation (TBI) dose and fractionation on risk of subsequent malignant neoplasms (SMNs) in the era of reduced-intensity and nonmyeloablative conditioning regimens for hematopoietic cell transplantation (HCT). Among 4905 1-year survivors of allogeneic HCT for hematologic malignancies (N = 4500) or nonmalignant disorders (N = 405) who received transplants between 1969 and 2014, we identified 581 SMNs (excluding squamous and basal cell of skin) in 499 individuals. With a median length of follow-up of 12.5 years, the cumulative incidence of SMNs by 30 years after HCT was 22.0%. Compared with age-, sex-, and calendar year–matched Surveillance, Epidemiology, and End Results (SEER) population rates, the standardized incidence ratio (SIR) of SMNs was increased 2.8-fold. The highest SIRs were for SMNs of bones (SIR, 28.8), oral cavity (SIR, 13.8), skin (SIR, 7.3), central nervous system (SIR, 6.0), and endocrine organs (SIR, 4.9). The highest excess absolute risks (EARs) were seen with breast cancer (EAR, 2.2) and cancers of the oral cavity (EAR, 1.5) and skin (EAR, 1.5) per 1000 person-years. The highest incidence of SMNs was in survivors exposed to unfractionated (600-1000 cGy) or high-dose fractionated (1440-1750 cGy) TBI. For patients receiving low-dose TBI, the incidence was comparable to myeloablative chemotherapy alone, although still twofold higher than in the general population. These data demonstrate a strong effect of TBI dose, dose fractionation, and risk of SMNs after HCT. The cumulative incidence of SMNs increases with follow-up time; thus, HCT survivors require lifetime monitoring for early detection and effective therapy of SMNs.

Sleep and timing of death by suicide among U.S. Veterans 2006-2015: analysis of the American Time Use Survey and the National Violent Death Reporting System.

Suicide is a top public health priority, and U.S. Veterans are recognized to be at particularly elevated risk. Sleep disturbances are an independent risk factor for suicide; recent empirical data suggest that nocturnal wakefulness may be a key mechanism underlying this association. Given higher rates of sleep disturbances among U.S. Veterans compared with civilians, we examined associations between nocturnal wakefulness and timing of death by suicide in U.S. Veterans and civilians to determine whether temporal suicide patterns differed. The American Time Use Survey and the National Violent Death Reporting System were analyzed (2006-2015) to determine whether sleep and temporal suicide patterns differed between age-stratified groups (18-39, 40-64, and ≥65) of U.S. Veterans and civilians. Observed temporal suicide patterns were reported and standardized incidence ratios (SIRs) calculated to compare the percentage of suicides observed with those expected, given the proportion of the population awake, across clock hours. The raw proportion of Veteran suicides peaks between the hours of 1000-1200; however, the peak prevalence of suicide after accounting for the population awake is between 0000 and 0300 hr (p < .00001, ϕ = .88). The highest SIR was at midnight; U.S. Veterans were eight times more likely to die by suicide than expected given the population awake (SIR = 8.17; 95% CI = 7.45-8.94). Nocturnal wakefulness is associated with increased risk for suicide in U.S. Veterans. Overall patterns of observed suicides by clock hour were similar between U.S. Veterans and civilians. However, Veteran-specific SIRs suggest differences in magnitude of risk by clock hour across age groups. Future research examining female and Post-9/11 U.S. Veterans is warranted.

Geographic surveillance of community associated MRSA infections in children using electronic health record data

BackgroundCommunity- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses.MethodsAn epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus.ResultsCA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p < 0.0001); this finding persisted at the block group level (p < 0.001) along with household crowding (p < 0.001). The youngest category of age (< 4 years) also had increased risk for CA-MRSA (aOR 1.65, 95%CI 1.48, 1.83, p < 0.0001). CA-MRSA encompasses larger areas with higher SIRs compared to non-resistant forms and were found in block groups with higher proportion of blacks (r = 0.517, p < 0.001), younger age (r = 0.137, p < 0.001), and crowding (r = 0.320, p < 0.001).ConclusionsIn the Atlanta MSA, the risk for CA-MRSA is associated with neighborhood-level measures of racial composition, household crowding, and age of children. Neighborhoods which have higher proportion of blacks, household crowding, and children < 4 years of age are at greatest risk. Understanding spatial relationship at a community level and how it relates to risks for antibiotic resistant infections is important to combat the growing numbers and spread of such infections like CA-MRSA.

Bidirectional relationship between systemic lupus erythematosus and non-Hodgkin's lymphoma: a nationwide population-based study.

We conducted this nationwide population-based study in Taiwan to investigate whether there is a bidirectional relationship between SLE and non-Hodgkin's lymphoma (NHL). Using the National Health Insurance Research Database of Taiwan, we identified 16 417 patients with new-onset SLE without previous cancer and 25 069 patients with new-onset NHL without previous SLE as two non-overlapping cohorts from 1998-2012, and followed them until 2013. Standardized incidence ratio (SIR) for NHL in the patients with SLE and SIR for SLE in the patients with NHL were compared with the general population. Among the 16 417 patients with SLE, 512 developed cancers, including 34 with NHL. The highest SIR was that for NHL (SIR 4.2, 95% CI 2.9, 5.9) in site-specific cancer risk analysis. Among the 25 069 patients with NHL, 14 developed SLE, and the SIR was also increased (SIR 2.0, 95% CI 1.1, 3.4). The SIRs of the patients with SLE to develop NHL and the patients with NHL to develop SLE were both highest within the first year after the diagnosis of each disease. This nationwide population-based study is the first study to report a bidirectional relationship between SLE and NHL. This finding may suggest being alert for the patients with SLE or NHL who have early sings of the other disease in clinical care.

Risk factors for metachronous bilateral renal cell carcinoma: A surveillance, epidemiology, and end results analysis.

Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database. Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year after primary diagnosis. We performed a competing risks analysis to evaluate associations between clinicopathologic factors and metachronous, bilateral RCC. Cumulative incidence and standardized incidence ratios (SIRs) were calculated. There were 80,403 cases of RCC identified, with a median follow-up of 8.3 years; of these, 1063 (1.3%) developed metachronous, contralateral RCC (median of 6 years after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.5%, 3.1%, and 4.7%, respectively. An increased risk was observed among men (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.20-1.55), blacks (HR, 2.00; 95% CI, 1.71-2.33), and those with papillary histology (HR, 1.72; 95% CI, 1.41-2.10). Risk of metachronous disease decreased with increasing age at primary diagnosis (HR per 1-year increase, 0.97; 95% CI, 0.96-0.97). The SIRs were highest among those diagnosed at a younger age and remained elevated even after extended follow-up (>10 years). Our findings suggest that the cumulative incidence of metachronous, contralateral RCC may be higher than previously reported. Younger age, black race, papillary histology, and male sex increase the risk of metachronous, contralateral RCC development. The high SIRs seen in all demographic groups may support a rationale for lifelong surveillance, especially in high-risk subgroups with early disease onset.

Trends in the Risk of Second Primary Malignancies (SPMs) Among Survivors of Chronic Lymphocytic Leukemia(CLL)

Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this.Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis.Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p<0.001). Moreover increased HRs were also observed for 1983-1992 and 1993-2002 time periods (Fig. 1)Conclusions: With improving therapeutics for cancer treatment, survivorship is improving as well and the risk of SPMs needs to be better understood and addressed. This is truer for CLL, where majority of patients have a favorable survival. The risk of SPMs was 20% higher in CLL survivors than in the general population and was most prominent in the survivors aged 15-49 years at the time of CLL diagnosis. The risk of individual malignancies may be heterogenous but there has been an increase in risk of SPMs over time, mainly due to an increase of secondary hematological malignancies in recent years. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL. DisclosuresAilawadhi:Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.

Occupation and risk of cancer of the renal pelvis in Nordic countries.

To evaluate occupational variation in the incidence of the malignant neoplasm of the renal pelvis in the population of the Nordic countries: Denmark, Iceland, Finland, Norway and Sweden. The study cohort comprised 14.9 million individuals. Data on occupational history were obtained from national censuses. Standardized incidence ratios (SIRs) were calculated for each occupation. The highest SIRs were found in seamen (1.51, 95% confidence interval [CI] 1.23-1.82), printers (1.39, 95% CI 1.11-1.71), welders (1.37, 95% CI 1.03-1.78), and public safety workers (1.35, 95% CI 1.12-1.62). The lowest SIRs were observed in forestry workers (0.47, 95% CI 0.35-0.62), gardeners (0.72, 95% CI 0.62-0.83) and woodworkers (0.81, 95% CI 0.72-0.91). The study suggests that there is an association between profession and risk of malignancy of the renal pelvis. The possible associations between exposure to asbestos, heavy metals and welding fumes, and risk of developing the disease should be studied further.

Secondary Cancers in Hodgkin Lymphoma: A Comprehensive Analysis of Incidence and Trends in Survivors

OBJECTIVES: The impact of treatment modifications including replacement of alkylating agents based regimens and improvement in the practices of radiation oncology on the risk of secondary cancers (SCs) in Hodgkin's lymphoma (HL) survivors is unknown in the United States (U.S.). This study analyzed the trends of secondary cancer risks among the survivors of HL in the U.S.METHODS: The HL patients diagnosed during 1973-2014 were identified from the Surveillance, Epidemiology and End results (SEER) database. Due to differences in the treatment practices in HL, the whole cohort was divided into three time-periods: 1973-1986, 1987-2000 and 2001-2014. We compared the risk of SCs in the HL patients with the risk expected in the U.S. general population over the three study periods.RESULTS: With a follow-up of 23,864 HL survivors for 284,730 person-years (PY), 3260 secondary cancers were diagnosed, with standardized incidence ratio (SIR) of 1.97 (95% CI, 1.9-2.04) which resulted in 56.56 excess cancers per 10,000 person-years. SIR for any SCs in women (SIR 2.17; 95% CI 2.06-2.28) was significantly higher than in the men (SIR 1.84; 95% CI 1.75-1.92). The highest SIRs were observed for AML (SIR, 9.9; 95%CI, 8.3-11.9), NHL (SIR, 5.8; 95% CI, 5.3-6.4) and salivary gland tumors (SIR, 6.04; 95% CI, 4-8.8) while lung cancer (23.6%) and breast cancer (27.4%) contributed most to the excess risk in males and females respectively. The SIR for any SCs was maximum in the period after 15 to 20 years from the diagnosis of HL and remained high for more than 20 years after the diagnosis of HL (SIR for ≥ 20 years, 2.34; 95% CI, 2.19 to 2.5). A statistically significant decrease in the overall SIRs of SCs was observed in HL patients diagnosed during 1987-2000 (SIR 1.82 95% CI 1.72-1.93) and 2001-2014 (SIR 1.66 95% CI 1.51-1.82) as compared to the patients diagnosed in 1973-1986 (SIR 2.24 95% CI 2.13-2.35). (Figure 1) The decline in the overall SIR was mostly due to decline in the digestive tract and breast cancers. The SIRs of most of the other solid tumors and hematological malignancies including individual risks for NHL and AML did not decrease in the more recent study periods. Moreover, the decline in the SIRs of solid tumors was noticed only in the patients age below 60 years old. The female patients diagnosed in the most recent period were at lower risk of developing breast cancers (SIR 0.56 95% CI 0.34-0.86) as compared to the general population. The decline in the risk for secondary cancers was observed only after 10 years from the diagnosis of HL. After making adjustments for age, gender and race, patients diagnosed during 1973-1986 were at 12% higher risk of developing SCs (HR 1.12 95% CI 1.03-1.23 p=0.01) as compared to the patients diagnosed during 1987-2000. The hazard ratio for developing SCs in the patients diagnosed during 2001-2014 was not different from the patients diagnosed during 1987-2000 (HR 1.02 95% CI 0.9-1.2 p=0.74).CONCLUSIONS: Although, the overall risk of secondary cancers in patients with Hodgkin's lymphoma has declined after the modifications in Hodgkin's lymphoma treatment, apart from the digestive tract and breast cancers the risk has not changed significantly at most of the individual sites. The risk of secondary cancers is still 70% higher than the general population and is maximum 15-20 years from the diagnosis of Hodgkin's lymphoma. Thus close follow up with active surveillance for secondary cancers is crucial for the long term survivors of Hodgkin's lymphoma. [Display omitted] DisclosuresAilawadhi:Novartis: Consultancy, Honoraria; Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe.

BackgroundChildhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer.MethodsWe pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated.ResultsOverall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma.ConclusionsFor the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.

Menopausal hormone therapy and cancer risk: An overestimated risk?

AimWe aimed to assess the overall cancer risk among contemporary menopausal hormone therapy (MHT) users in Sweden and the risk for different cancer types. MethodsA nationwide Swedish population-based cohort study including all 290,186 women aged ≥ 40 years having used systemic MHT during the study period (July 2005 and December 2012), compared with the Swedish female background population. MHT ever-use (all MHT, oestrogen-only MHT [E-MHT] and oestrogen plus progestin MHT [EP-MHT]) was based on the nationwide Prescribed Drug Registry. Cancer diagnoses were grouped into 16 different anatomical locations, for which standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. ResultsThe SIR of any cancer was 1.09 (95% CI: 1.07–1.11) following ever MHT, 1.04 (95% CI: 1.01–1.06) for E-MHT and 1.14 (95% CI: 1.12–1.17) for EP-MHT. The highest SIR was found for EP-MHT among users aged ≥70 years (SIR = 1.33, 95% CI: 1.26–1.40). The risk for invasive breast, endometrial or ovarian cancer combined was increased for any MHT (SIR = 1.31, 95% CI: 1.28–1.34). The risk of invasive breast cancer was increased following MHT and increased with age for EP-MHT users. The risk of gastrointestinal cancers combined was decreased (SIR = 0.90, 95% CI: 0.86–0.94), particularly the oesophagus (SIR = 0.81, 95% CI: 0.64–1.00), liver (SIR = 0.81, 95% CI: 0.65–0.99) and colon (SIR = 0.90, 95% CI: 0.84–0.95). ConclusionsMHT, notably EP-MHT, was associated with a limited increase in overall cancer risk. The increased risk of female reproductive organ cancers was almost balanced by a decreased risk of gastrointestinal cancers.

Elevated risk of human papillomavirus-related second cancers in survivors of anal canal cancer.

Over the last decade, the causal link between human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA) has been well described. Because HPV infection in one site is often associated with other sites of infection, it then follows that patients with SCCA may have an increased risk of additional HPV-related cancers. Identifying and targeting at-risk sites through cancer screening and surveillance may help to guide best practices. The current study sought to ascertain sites and risk of HPV-related second primary malignancies (SPMs) in survivors of SCCA. Using population-based data from 1992 through 2012, the authors identified patients with SCCA and determined their risk of HPV-related SPMs, including anal, oral, and genital cancers. Standardized incidence ratios (SIRs), defined as observed to expected cases, were calculated to determine excess risk. Of 10,537 patients with SCCA, 416 developed HPV-related SPMs, which corresponded to an overall SIR of 21.5 (99% confidence interval [99% CI], 19.0-24.2). Men were found to have a higher SIR (35.8; 99% CI, 30.7-41.6) compared with women (12.8; 99% CI, 10.4-15.5). SIRs for a second SCCA were markedly higher in men (127.5; 99% CI, 108.1-149.2) compared with women (47.0; 99% CI, 34.7-62.1), whereas SIRs for oral cavity and pharyngeal cancers were elevated in men (3.1; 99% CI, 1.5-5.7) and women (4.4; 99% CI, 1.5-9.7). SIRs for sex-specific sites also were elevated, with male genital cancers having an SIR of 19.6 (99% CI, 8.7-37.6) and female genital cancers an SIR of 8.3 (99% CI, 6.1-11.0). Patients with index SCCA are at an increased risk of subsequent HPV-related SPMs. The elevated risk is most striking in patients with second primary SCCAs; however, the risk of second cancers also appears to be increased in other HPV-related sites. Cancer 2017;123:4013-21. © 2017 American Cancer Society.

Secondary solid tumors in patients younger than 55 with chronic lymphocytic leukemia (CLL).

10083 Background: Patients with CLL are at an increased risk of secondary solid tumors. Few studies have looked at this risk in patients &lt; 55, despite research suggesting that this is a distinct cohort with a longer overall survival. What data does exist has yielded variable results in limited populations. In light of this, our study utilized the SEER registry to look at secondary solid tumors in patients &lt; 55 with CLL. Methods: 4559 patients 15-54 years old with CLL were identified in the SEER registry between 1973 and 2013. Cancer risk was assessed using standardized incidence ratios (SIR) of observed (O) and expected (E) cancers. 95% confidence intervals (CI) were calculated assuming a Poisson distribution. Results where the CI = 1 were excluded. Results: 498 patients (O/E = 1.4) developed a secondary solid tumor after CLL with a mean age at diagnosis of 48.8 and 59.9 years for CLL and a second tumor, respectively. Higher than expected risk was seen in lip (O/E = 7.5), non-epithelial skin (O/E = 5.4), salivary (O/E = 4.8), mesothelioma (O/E = 4.4), melanoma (O/E = 3.1), lung (O/E = 2.4), and kidney (O/E = 1.7) cancers. Uterine cancer had a lower risk (O/E = 0.4). Stratifying the cohort by gender and race found that lip cancer in whites (O/E = 7.6) and men (O/E = 7.3), descending colon cancer (O/E = 13.3) in blacks and ureter cancer (O/E = 19.8) in women posed the highest risks. Lung cancer was the most prevalent among all groups. Secondary tumor risk was elevated in the &lt; 1, 1-5, 5-10, and 10-15 years after diagnosis with CLL (O/E = 2.3, 1.4, 1.5, and 1.4, respectively). The cancers with the highest SIR in each period were thyroid ( &lt; 1 year, O/E = 9.2), lung (1-5 years, O/E = 3.1), nose/ear (5-10 years, O/E = 11.8), and lip (10-15 years, O/E = 15.6). In 4459 patients &gt; 55 (O/E = 1.1), Kaposi sarcoma (O/E = 4.9), non-epithelial skin (O/E = 3.6), salivary (O/E = 2.8), melanoma (O/E = 2.1), nose/ear (O/E = 2.0), lip (O/E = 1.7), soft tissue (O/E = 1.6), lung (O/E = 1.4), kidney (O/E = 1.3), and colon cancers (O/E = 1.2) were significant. Conclusions: Patients &lt; 55 have a unique tumor profile and greater risk of secondary solid tumors compared to patients &gt; 55. This risk differs on the basis of gender, race, and survival time. Further research may help influence screening guidelines.

New primary lung cancers after a head and neck cancer: The impact of radiation therapy and latency period on risk.

10015 Background: Patients with head and neck cancer (HNC) have an increased risk of developing a new primary lung cancer (NPLC). Our objective was to assess the critical latency period after HNC when the risk for a NPLC was highest and to see if radiation therapy (XRT) had an impact on this risk. Methods: This was a population based study of patients with HNC in the Surveillance, Epidemiology, and End Results (SEER) database. The risk of NPLC was calculated using standardized incidence ratios (SIR) and from this, the number needed to screen (NNS) was extrapolated. The cohort was separated by delivery of XRT and latency period of the NPLC. Results: There were a total of 4,209 NPLC from the cohort of 85,154 HNC patients. The SIR, NNS, observed/expected number of NPLC for both the no XRT and XRT groups are shown in table 1. As compared to the no XRT group, the XRT group had higher SIR and lower NNS values across all latency periods. The highest SIR for both the no XRT and XRT groups came between 1 and 3 years. Conclusions: In patients with HNC, the risk of developing a NPLC is associated with receiving XRT. This risk is highest within 10 years of the initial HNC diagnosis. The NNS was especially low for the XRT group, less than 100 for most latency periods. Since low dose computed tomography scans for lung cancer screening in smokers has a NNS of 217, screening for these patients should be considered, especially within 10 years of the primary HNC diagnosis. This may contribute to better survivorship care in these patients. [Table: see text]

Cancer risk in patients with hepatitis C virus infection: apopulation-based study in Sweden.

Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios (SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20–40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59–0.90) and melanoma (0.50; 95% CI: 0.30–0.79). A significant sex‐difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36–45.45 for men and 27.21; 95% CI: 21.90–33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow‐up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage.

The incidence and mortality of lip and oral cavity cancer and its relationship to the 2012 Human Development Index of Asia

Introduction: Lip and oral cavity cancer is one of the most prevalent cancers in Asia and considered to be a major public health problem due to the low survival rate. Because of the importance of access to information about this cancer (including incidence, mortality rate and relation to socioeconomic indicators), this study aims at investigating the incidence and mortality of lip and oral cavity cancer and its relationship with the Human Development Index (HDI) of Asia (from 2012).&#x0D; Method: This study was an ecological study in Asia for assessment of the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with the HDI and its components which include: life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. Data on the standardized incidence ratio (SIR) and the standardized mortality ratio (SMR) for every Asian country for the year 2012 were obtained from the global cancer project and data on the HDI and its components were extracted from the World bank site. &#x0D; We used a bivariate method for assessment of the correlation between the SIR and SMR with the HDI and its individual components. Statistical significance was assumed if P&lt;0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.).&#x0D; Results: A total incidence of 162,506 cases and 95,005 deaths were recorded in Asian countries in 2012. Countries with the highest SIR (per 100,000) were the following: Maldives (11), Sri Lanka (10.3), Pakistan (9.8), Bangladesh (9.4), and India (7.2). The highest SMR was observed in the following countries: Pakistan (5.9), Bangladesh (5.6), Afghanistan (5.1), India (4.9), and Maldives (4.1). The correlation between SIR of lip and oral cavity cancer and HDI was -0.378 (p=0.010), with life expectancy at birth at -0.324 (p=0.028), mean years of schooling at -0.283 (p=0.057), and level of income per each person of the population at -0.279 (p=0.060). Moreover, the correlation was -0.664 (p≤0.001) between SMR and HDI.&#x0D; Conclusion: A significant reverse correlation was seen between the incidence and mortality rate of lip and oral cavity cancer and the HDI in Asia. The incidence and mortality of this type of cancer was high in developing or less developed countries. &#x0D;

Cancer and mTOR Inhibitors in Transplant Recipients.

Malignancy is the second most common single cause of death observed in organ transplant recipients. The excess cancer risk is related to intensity and duration of immunosuppressive therapy and inversely to recipient age. Immunodeficiency and (chronic/oncogenic) viral infections together constitute a major risk. Nonmelanoma skin cancer, Kaposi sarcoma, and posttransplant lymphoproliferative disease have standardized incidence ratios exceeding 10- or 50-fold. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used after organ transplantation with potential advantages in virus-associated posttransplant malignancies as well as anti-cancer properties. Despite a seemingly clear mechanism of action and solid rationale for their use in cancer therapy, mTORis have met only modest success rates in clinical trials with advanced malignancies except for specific tumors, such as Kaposi sarcoma and mantle cell lymphoma. Because mTORis are primarily cytostatic, not cytotoxic, the observed clinical efficacy is a reflection of disease stabilization rather than tumor regression. Nonmelanoma skin cancers, in particular cutaneous squamous cell carcinoma, have the highest standardized incidence ratios in transplant recipients. Recent meta-analyses and randomized trials on secondary prevention of squamous cell carcinoma observed a reduction in cumulative tumor load, suggesting most benefit to be gained by early conversion to an mTOR inhibitor-based maintenance regime. There is ongoing debate on the mechanisms involved including withdrawal of the carcinogenic effects of calcineurin inhibitors and/or their impact on chronic (oncogenic) viral infections. At present, there is, however, insufficient evidence for the primary use of mTORis as protective agents against most other cancer types.

Epidemiology of idiopathic nephrotic syndrome in children: endemic or epidemic?

The etiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been reported to be associated with INS onset and relapse. The aim of this study was to describe the epidemiology of a population-based cohort of children with INS and propose a spatiotemporal analysis. All children aged 6months to 15years with INS onset between December 2007 and May 2010 and living in the Paris area were included in a prospective multicenter study. Demographic and clinical features at diagnosis and 2years were collected. INS was diagnosed in 188 children, 93% of whom were steroid sensitive. Annual incidence was 3.35/100,000 children. Standardized incidence ratio (SIR) was higher in one of the eight counties: Seine-Saint-Denis, with SIR 1.43 [95%confidence interval (CI) 1.02-1.95]. A spatial cluster was further identified with higher SIR 1.36 (95 % CI 1.09-1.67). Temporal analysis within this overincidence area showed seasonal variation, with a peak during the winter period (p <0.01). In addition, partition of the Paris area into quintiles of the population showed that the average delay of occurrence, with regard to the first study case, followed a longitudinal progression (p <0.0001). The clustering of cases, the seasonal variation within this particular area, and the progression over the Paris area altogether suggest that INS may occur on an epidemic mode.