Correction: Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0278354.].

Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study.

This study examines childhood cancer survival rates and prognostic factors related to survival in the majority Hispanic population of South Texas. The population-based cohort study used Texas Cancer Registry data (1995-2017) to examine survival and prognostic factors. Cox proportional hazard models and Kaplan-Meier survival curves were used for survival analyses. The 5-year relative survival rate for 7,999 South Texas cancer patients diagnosed at 0-19 years was 80.3% for all races/ethnicities. Hispanic patients had statistically significant lower 5-year relative survival rates than non-Hispanic White (NHW) patients for male and female together diagnosed at age≥5 years. When comparing survival among Hispanic and NHW patients for the most common cancer, acute lymphocytic leukemia (ALL), the difference was most significant in the 15-19 years age range, with 47.7% Hispanic patients surviving at 5 years compared to 78.4% of NHW counterparts. The multivariable-adjusted analysis showed that males had statistically significant 13% increased mortality risk than females [hazard ratio (HR): 1.13, 95% confidence interval (CI):1.01-1.26] for all cancer types. Comparing to patients diagnosed at ages 1-4 years, patients diagnosed at age < 1 year (HR: 1.69, 95% CI: 1.36-2.09), at 10-14 year (HR: 1.42, 95% CI: 1.20-1.68), or at 15-19 years (HR: 1.40, 95% CI: 1.20-1.64) had significant increased mortality risk. Comparing to NHW patients, Hispanic patients showed 38% significantly increased mortality risk for all cancer types, 66% for ALL, and 52% for brain cancer. South Texas Hispanic patients had lower 5-year relative survival than NHW patients especially for ALL. Male gender, diagnosis at age<1 year or 10-19 years were also associated with decreased childhood cancer survival. Despite advances in treatment, Hispanic patients lag significantly behind NHW patients. Further cohort studies in South Texas are warranted to identify additional factors affecting survival and to develop interventional strategies.

Breastfeeding practices and associations with pregnancy, maternal and infant characteristics in Australia: a cross-sectional study.

BACKGROUND: Exclusive breastfeeding to six months of age is a major global public health priority. Several characteristics are known to be associated with early cessation of breastfeeding, however, limited evidence exists regarding whether women's reported reasons for cessation are associated with maternal, pregnancy and infant characteristics. The aims of this study were to: i) describe women's reported intention to breastfeed and their subsequent breastfeeding practices; ii) describe women's reported reasons for breastfeeding cessation prior to the infant being five months of age; and iii) examine associations between these factors and maternal, pregnancy and infant characteristics. METHODS: Telephone and online surveys were conducted between October 2019 and April 2020 with 536 women who had given birth in the previous eight to 21 weeks at four public maternity services in Australia. RESULTS: The majority of women intended to (94%), and did, initiate (95%) breastfeeding. At the time the survey was conducted, 57% of women were exclusively breastfeeding. Women who: had less than University level education, had a pre-pregnancy BMI in the overweight or obese category, and who smoked tobacco at the time of the survey had lower odds of exclusively breastfeeding. The most common self-reported reasons for breastfeeding cessation were breastfeeding challenges (47%) and low milk supply (40%). Women aged 26-35 years and 36 + years had greater odds of reporting breastfeeding cessation due to low milk supply (OR = 2.92, 95% CI: 1.11, 7.66; OR = 5.57, 95% CI: 1.70, 18.29) compared to women aged 18-25 years. While women who had completed a TAFE certificate or diploma had lower odds of reporting this as a reason for breastfeeding cessation (OR = 0.28; 95% CI: 0.11, 0.73) compared to women who had University level education. There were no other significant associations found between characteristics and reasons for ceasing breastfeeding. CONCLUSIONS: The most common reasons for breastfeeding cessation may be modifiable through the provision of breastfeeding support in the early postpartum period, with such support being tailored to women's age and level of education. Such support should aim to increase women's self-efficacy in breastfeeding, and be provided from the antenatal period and throughout the first six months postpartum.

The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

STUDY QUESTION: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer? SUMMARY ANSWER: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects. WHAT IS KNOWN ALREADY: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved. STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer. LIMITATIONS, REASONS FOR CAUTION: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children. WIDER IMPLICATIONS OF THE FINDINGS: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Assessment of Birth Defects and Cancer Risk in Children Conceived via In Vitro Fertilization in the US.

Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF). Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally. Design, Setting, and Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020. Exposures: Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries. Main Outcomes and Measures: Cancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups. Results: A total of 1 000 639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52 776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group. Conclusions and Relevance: This study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally.

Association of In Vitro Fertilization With Childhood Cancer in the United States.

Importance: In vitro fertilization (IVF) is associated with birth defects and imprinting disorders. Because these conditions are associated with an increased risk of childhood cancer, many of which originate in utero, descriptions of cancers among children conceived via IVF are imperative. Objective: To compare the incidence of childhood cancers among children conceived in vitro with those conceived naturally. Design, Setting, and Participants: A retrospective, population-based cohort study linking cycles reported to the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System from January 1, 2004, to December 31, 2012, that resulted in live births from September 1, 2004, to December 31, 2013, to the birth and cancer registries of 14 states, comprising 66% of United States births and 75% of IVF-conceived births, with follow-up from September 1, 2004, to December 31, 2014. The study included 275 686 children conceived via IVF and a cohort of 2 266 847 children, in which 10 births were randomly selected for each IVF birth. Statistical analysis was performed from April 1, 2017, to October 1, 2018. Exposure: In vitro fertilization. Main Outcomes and Measures: Cancer diagnosed in the first decade of life. Results: A total of 321 cancers were detected among the children conceived via IVF (49.1% girls and 50.9% boys; mean [SD] age, 4.6 [2.5] years for singleton births and 5.9 [2.4] years for multiple births), and a total of 2042 cancers were detected among the children not conceived via IVF (49.2% girls and 50.8% boys; mean [SD] age, 6.1 [2.6] years for singleton births and 4.7 [2.6] years for multiple births). The overall cancer rate (per 1 000 000 person-years) was 251.9 for the IVF group and 192.7 for the non-IVF group (hazard ratio, 1.17; 95% CI, 1.00-1.36). The rate of hepatic tumors was higher among the IVF group than the non-IVF group (hepatic tumor rate: 18.1 vs 5.7; hazard ratio, 2.46; 95% CI, 1.29-4.70); the rates of other cancers did not differ between the 2 groups. There were no associations with specific IVF treatment modalities or indication for IVF. Conclusions and Relevance: This study found a small association of IVF with overall cancers of early childhood, but it did observe an increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility. Continued follow-up for cancer occurrence among children conceived via IVF is warranted.

Embryo banking among women diagnosed with cancer: a pilot population-based study in New York, Texas, and Illinois.

PURPOSE: The purpose of the present study is to estimate the proportion of women with cancer who return to use the embryos that they have banked and to compare this proportion to that of women without cancer who bank embryos. METHODS: This is a cohort study of three groups of women from New York, Texas, and Illinois who used embryo banking in their first assisted reproductive technology (ART) treatment cycle: two groups with cancer (222 women without an infertility diagnosis and 48 women with an infertility diagnosis) and a control group without cancer (68 women with the infertility diagnosis of male factor only). Women were included only if their first ART cycle reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) occurred between 2004 and 2009. Cancer cases were identified from each State Cancer Registry from 5 years prior to initiation of ART treatment to 6 months post-initiation; mean follow-up after the first ART cycle was 2.0 years. RESULTS: Women with cancer without an infertility diagnosis returned for a subsequent ART cycle at a lower rate (10.8 %) than those with an infertility diagnosis (31.3 %, p = 0.0010) or the control group (85.3 %, p < 0.0001). Among those who returned for a subsequent cycle, women with cancer waited a longer time to return (14.3 months without an infertility diagnosis and 8.3 months with an infertility diagnosis, p = 0.13) compared to the control group (2.8 months, p = 0.0007). The live birth rate among women who did not utilize embryo banking in their second cycle did not differ significantly across the three study groups, ranging from 25.0 and 42.9 % for women with cancer with and without an infertility diagnosis, respectively, to 36.2 % for women in the control group. CONCLUSIONS: Women with cancer without an infertility diagnosis are either less likely to return for subsequent treatment or will wait a longer time to return than women with an infertility diagnosis or those that do not have cancer. A longer-term study is necessary to assess whether these women return to use their frozen embryos after cancer treatment or are able to spontaneously conceive and if those subsequent pregnancies are adversely affected by the cancer diagnosis or therapy.

Assisted reproductive technology use and outcomes among women with a history of cancer.

STUDY QUESTION: How do the assisted reproductive technology (ART) outcomes of women presenting for ART after cancer diagnosis compare to women without cancer? SUMMARY ANSWER: The likelihood of a live birth after ART among women with prior cancer using autologous oocytes is reduced and varies by cancer diagnosis but is similar to women without cancer when donor oocytes are used. WHAT IS KNOWN ALREADY: Premenopausal patients faced with a cancer diagnosis frequently present for fertility preservation. STUDY DESIGN, SIZE, DURATION: Population-based cohort study of women treated with ART in NY, TX and IL, USA. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with their first ART treatment between 2004 and 2009 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database and linked to their respective State Cancer Registries based on name, date of birth and social security number. Years were rounded, i.e. year 1 = 6-18 months before treatment. This study used reports of cancer from 5 years, 6 months prior to treatment until 6 months after first ART treatment. Women who only presented for embryo banking were omitted from the analysis. The likelihood of pregnancy and of live birth with ART using autologous oocytes was modeled using logistic regression, with women without prior cancer as the reference group, adjusted for woman's age, parity, cumulative FSH dosage, infertility diagnosis, number of diagnoses, number of ART cycles, State of residency and year of ART treatment. Results of the modeling are reported as adjusted odds ratios (AORs) and (95% confidence intervals). MAIN RESULTS AND THE ROLE OF CHANCE: The study population included 53 426 women; 441 women were diagnosed with cancer within 5 years prior to ART cycle start. Mean (±SD) age at cancer diagnosis was 33.4 ± 5.7 years; age at start of ART treatment was 34.9 ± 5.8 for women with cancer compared with 35.3 ± 5.3 years for women without cancer (P = 0.03). Live birth rates among women using autologous oocytes differed substantially by cancer status (47.7% without cancer versus 24.7% with cancer, P < 0.0001), and cancer diagnosis (ranging from 53.5% for melanoma to 14.3% for breast cancer, P < 0.0001. The live birth rates among women using donor oocytes did not vary significantly by cancer status (60.4% for women with any cancer versus 64.5% for women without cancer), or by cancer diagnosis (ranging from 57.9% for breast cancer to 63.6% for endocrine cancer). Women with breast cancer make up about one-third of all cancers in this cohort. Among women with breast cancer, 2.8% of the 106 women who underwent ART within 6 months of being diagnosed with cancer used donor oocytes compared with 34.8% of the 46 women who received ART treatment a longer time after being diagnosed with cancer (P < 0.0001). We conjecture that the former group were either unaware that they had cancer or decided to undergo ART therapy prior to cancer treatment. However, their live birth rate was only 11.7% compared with 28.8%, the overall live birth rate for all women with cancer using autologous oocytes (P < 0.0001). The live birth rate for women diagnosed with breast cancer more than 6 months before ART (23.3%) did not differ significantly from the overall live birth rate for cancer (P = 0.49). If this difference is substantiated by a larger study, it would indicate a negative effect of severe recent illness itself on ART success, rather than the poor outcome being only related to the destructive effects of chemotherapies on ovarian follicles. Alternatively, because of the short time difference between cancer diagnosis and ART treatment, these pre-existing cancers may have been detected due to the increased medical surveillance during ART therapy. In women who only used autologous oocytes, women with prior cancers were significantly less likely to become pregnant and to have a live birth than those without cancer (adjusted odds ratio (AOR): 0.34, [95% confidence interval (CI): 0.27, 0.42] and 0.36 [0.28, 0.46], respectively). This was also evident with specific cancer diagnoses: breast cancer (0.20 [0.13, 0.32] and 0.19 [0.11, 0.30], respectively), cervical cancer (0.36 [0.15, 0.87] and 0.33 [0.13, 0.84], respectively) and all female genital cancers (0.49 [0.27, 0.87] and 0.47 [0.25, 0.86], respectively). Of note, among women with cancer who became pregnant, their likelihood of having a live birth did not differ significantly from women without cancer (85.8 versus 86.7% for women using autologous oocytes, and 85.3 versus 86.9% for women using donor oocytes). LIMITATIONS, REASONS FOR CAUTION: Women may not have been residents of the individual States for the entire 5-year pre-ART period, and therefore some cancers may not have been identified through this linkage. As a result, the actual observed number of cancers may be an underestimate. In addition, the overall prevalence is low due to the age distributions. Also, because we restricted the pre-ART period to 5 years prior, we would not have identified women who were survivors of early childhood cancers (younger than age 13 years at cancer diagnosis), or who had ART more than 5 years after being diagnosed with cancer. Additional analyses are currently underway evaluating live birth outcomes after embryo banking among women with cancer prior to ART, cycles which were excluded from the analyses in this paper. Future studies are planned which will include more States, as well as linkages to vital records to obtain information on spontaneous conceptions and births, to further clarify some of the issues raised in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: Since the live birth rates using donor oocytes were not reduced in women with a prior cancer, but were reduced with autologous cycles, this suggests that factors acting in the pre- or peri-conceptional periods may be responsible for the decline. STUDY FUNDING/COMPETING INTERESTS: The study was funded by grant R01 CA151973 from the National Cancer Institute, National Institutes of Health, USA. B.L. is a research consultant for the Society for Assisted Reproductive Technology. All other authors report no conflict of interest.

Cancer in women after assisted reproductive technology.

OBJECTIVE: To evaluate the risk of cancer after assisted reproductive technology (ART) therapy. DESIGN: Longitudinal cohort study. SETTING: Not applicable. PATIENT(S): New York, Texas, and Illinois residents between 2004 and 2009, treated with ART, comprising cycles of 113,226 women, including 53,859 women without prior ART treatment, who were linked to their respective state cancer registries and whose cycles were reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Diagnosis of cancer, as reported to the state cancer registry; standardized incidence ratios (SIR) and their 95% confidence intervals, comparing the observed to expected cancer cases based on age-specific cancer rates in the general population of each state. RESULT(S): Among the cohort of women without prior ART therapy, hazard ratios (HR) and 95% confidence intervals (CI) were calculated for treatment parameters and reproductive history factors. The mean follow-up period was 4.87 years; among women without prior ART, 450 women developed 460 cancers. Women treated with ART had a statistically significantly lower risk for all cancers (for all women: SIR 0.78; CI, 0.73-0.83; women without prior ART: SIR 0.75; CI, 0.68-0.82), breast cancer, and all female genital cancers; a non-statistically-significant lower risk for endocrine and uterine cancer; and a non-statistically-significant higher risk for melanoma and ovarian cancer. Among women without prior ART, we found no statistically significant increased HR by parity, number of cycles, cumulative follicle-stimulating hormone dosage, or cycle outcome. CONCLUSION(S): Women initiating ART treatment have no greater risk for developing cancer after nearly 5 years of follow-up compared with the general population and with other women treated with ART.

All-cancers mortality rates approaching diseases of the heart mortality rates as leading cause of death in Texas.

OBJECTIVES: Diseases of the heart and malignant neoplasms (all-cancers) are the leading causes of death in the United States. The gap between the two has been closing in recent years. To assess the gap status in Texas and to establish a baseline to support evaluation efforts for the Cancer Prevention Research Institute of Texas, mortality data from 2006 to 2009 were analyzed. METHODS: Immediate cause of death data in Texas for the years 2006-2009 were analyzed and rates developed by sex, race/ethnicity, and four metropolitan counties. RESULTS: Overall, for the years 2006-2009, the age-adjusted mortality rates (AARs) among Texas residents for both diseases of the heart and all-cancers decreased; however, during this time frame, there was greater improvement in diseases of the heart AARs as compared with all-cancers AARs. For the four large metropolitan counties of Bexar, Dallas, Harris, and Travis, data were analyzed by sex and race/ethnicity, and 11 of the 12 largest percent mortality rate decreases were for diseases of the heart. CONCLUSIONS: Age-adjusted mortality rates among Texas residents from diseases of the heart are showing improvement as compared with the rates for all-cancers.

Muddy water? Variation in reporting receipt of breast cancer radiation therapy by population-based tumor registries.

PURPOSE: To evaluate, in the setting of breast cancer, the accuracy of registry radiation therapy (RT) coding compared with the gold standard of Medicare claims. METHODS AND MATERIALS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified 73,077 patients aged ≥66 years diagnosed with breast cancer in the period 2001-2007. Underascertainment (1 - sensitivity), sensitivity, specificity, κ, and χ(2) were calculated for RT receipt determined by registry data versus claims. Multivariate logistic regression characterized patient, treatment, and geographic factors associated with underascertainment of RT. Findings in the SEER-Medicare registries were compared with three non-SEER registries (Florida, New York, and Texas). RESULTS: In the SEER-Medicare registries, 41.6% (n=30,386) of patients received RT according to registry coding, versus 49.3% (n=36,047) according to Medicare claims (P<.001). Underascertainment of RT was more likely if patients resided in a newer SEER registry (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.60-1.80; P<.001), rural county (OR 1.34, 95% CI 1.21-1.48; P<.001), or if RT was delayed (OR 1.006/day, 95% CI 1.006-1.007; P<.001). Underascertainment of RT receipt in SEER registries was 18.7% (95% CI 18.6-18.8%), compared with 44.3% (95% CI 44.0-44.5%) in non-SEER registries. CONCLUSIONS: Population-based tumor registries are highly variable in ascertainment of RT receipt and should be augmented with other data sources when evaluating quality of breast cancer care. Future work should identify opportunities for the radiation oncology community to partner with registries to improve accuracy of treatment data.

Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals.

OBJECTIVES: HIV-infected people have elevated risk for lung cancer and higher mortality following cancer diagnosis than HIV-uninfected individuals. It is unclear whether HIV-infected individuals with lung cancer receive similar cancer treatment as HIV-uninfected individuals. DESIGN/METHODS: We studied adults more than 18 years of age with lung cancer reported to the Texas Cancer Registry (N = 156 930) from 1995 to 2009. HIV status was determined by linkage with the Texas enhanced HIV/AIDS Reporting System. For nonsmall cell lung cancer (NSCLC) cases, we identified predictors of cancer treatment using logistic regression. We used Cox regression to evaluate effects of HIV and cancer treatment on mortality. RESULTS: Compared with HIV-uninfected lung cancer patients (N = 156 593), HIV-infected lung cancer patients (N = 337) were more frequently young, non-Hispanic black, men, and with distant stage disease. HIV-infected NSCLC patients less frequently received cancer treatment than HIV-uninfected patients [60.3 vs. 77.5%; odds ratio 0.39, 95% confidence interval (CI) 0.30-0.52, after adjustment for diagnosis year, age, sex, race, stage, and histologic subtype]. HIV infection was associated with higher lung cancer-specific mortality (hazard ratio 1.34, 95% CI 1.15-1.56, adjusted for demographics and tumor characteristics). Inclusion of cancer treatment in adjusted models slightly attenuated the effect of HIV on lung cancer-specific mortality (hazard ratio 1.25; 95% CI 1.06-1.47). Also, there was a suggestion that HIV was more strongly associated with mortality among untreated than among treated patients (adjusted hazard ratio 1.32 vs. 1.16, P-interaction = 0.34). CONCLUSION: HIV-infected NSCLC patients were less frequently treated for lung cancer than HIV-uninfected patients, which may have affected survival.

Investigation of the binding pocket of human hematopoietic prostaglandin (PG) D2 synthase (hH-PGDS): a tale of two waters.

The inhibition of hH-PGDS has been proposed as a potential target for the development of anti-allergic and anti-inflammatory drugs. Herein we describe our investigation of the binding pocket of this important enzyme and our observation that two water molecules bind to our inhibitors and the enzyme. A series of compounds were prepared to the probe the importance of the water molecules in determining the binding affinity of the inhibitors to the enzyme. The study provides insight into the binding requirements for the design of potent hH-PGDS inhibitors.

Spectrum of cancer risk among US solid organ transplant recipients.

CONTEXT: Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. OBJECTIVE: To describe the overall pattern of cancer following solid organ transplantation. DESIGN, SETTING, AND PARTICIPANTS: Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS: The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). CONCLUSION: Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

Racial/ethnic disparities in survival among men diagnosed with prostate cancer in Texas.

BACKGROUND: To the authors' knowledge, few studies to date have examined racial differences in prostate cancer survival while controlling for socioeconomic status (SES). No such studies have examined this association in Texas, a large state with significant ethnic and racial diversity. The objective of this analysis was to determine whether racial disparities in survival for men diagnosed with prostate cancer in Texas from 1995 through 2002 remained after adjusting for SES, rural residence, and stage of disease. METHODS: A cohort of 87,449 men who were diagnosed with prostate cancer was identified from the Texas Cancer Registry. The SES measure was based on census tract data reflecting median household income, median home value, and percentages of men living below poverty, with a college education, and with a management or professional occupation. The 5-year survival rates were calculated using the Kaplan-Meier method and Cox proportional hazard modeling was used to estimate hazard ratios (HRs) for race and all-cause and disease-specific mortality. RESULTS: After adjusting for SES, age, stage of disease, tumor grade, year of diagnosis, and rural residence, both black and Hispanic men were more likely (adjusted HR [aHR], 1.70 [95% confidence interval (95% CI), 1.58-1.83] and aHR, 1.11 [95% CI, 1.02-1.20], respectively) to die of prostate cancer compared with white men. The pattern of survival disadvantage for black men held for those diagnosed with localized disease and advanced disease, and for those with an unknown stage of disease at diagnosis. CONCLUSIONS: Substantial racial disparities in prostate cancer survival were found for men in Texas. Future studies should incorporate treatment data as well as comorbid conditions because this information may explain noted survival disparities.

Cancer survival among Latinos and the Hispanic Paradox.

BACKGROUND: Cancer survival is a key indicator of the effectiveness and social justice of health services. However, little is known about cancer survival among Hispanics, how it varies by Hispanic subgroup (Mexicans, Puerto Ricans, Cubans, and Others), and how their survival patterns relate to the Hispanic Paradox. METHODS: We studied all 1.2 million cancer cases diagnosed during 1995-2003, in two states, Florida and Texas, according to three categories of outcome: highly fatal outcome, poor outcome, and moderate outcome. All were followed up until December 31, 2006. We calculated survival rates for each Hispanic subgroup, and using Cox regression, we studied the risk of death for each Hispanic subgroup compared with non-Hispanic Whites, adjusted for age, cancer site, and stage at diagnosis. RESULTS: Important differences in cancer survival were found according to Hispanic subgroup. For cancers of moderate outcome, the adjusted risk of death was higher among all Hispanic populations in comparison with non-Hispanic Whites: 6% higher for Cubans, 11% for Puerto Ricans, and 13% for US-born Mexicans. Foreign-born Mexicans, even with incomplete follow-up, had a 24% higher risk of death. For foreign-born Hispanics, except Cubans, the mortality follow-up of cancers of highly fatal outcome was insufficient, resulting in missing deaths and thus unrealistically high survival rates. CONCLUSIONS: No evidence of a Hispanic advantage was found in cancer survival. Improvement in mortality follow-up procedures for Latinos, especially for those without a valid social security number, is critical. By considering Hispanics as a whole rather than by subgroup, existing survival disparities are being missed.

County-level socioeconomic status and cancer rates in Texas, 2001-2005.

Previous studies have shown that a person's socioeconomic status (SES) (a proxy measure that can incorporate income, wealth, education, and occupation) is associated with cancer incidence and mortality. Examining variation in cancer rates by SES can help identify health disparities and target areas for cancer control activities. The Texas Cancer Registry (TCR) collects data on every newly diagnosed case of cancer in Texas, including personal and demographic data, but does not collect data related directly to SES. Using a county-level measure of SES determined by the 2000 US Census, we compared cancer incidence and mortality rates for selected cancer sites by counties categorized into Low, Intermediate, and High SES. The cancers examined in this analysis included lung, colorectal, female breast, prostate, cervical, and all cancers collected by TCR combined. Consistent with other studies, most incidence and mortality rates were lowest in the High SES counties. However, in general, the highest incidence and mortality rates were found in counties categorized as Intermediate SES, but patterns differed by cancer site and by race and ethnicity. This study provides additional evidence that geographically related SES is associated with cancer incidence and mortality.

Discovery of an Oral Potent Selective Inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS).

Hematopoietic prostaglandin D synthase (HPGDS) is primarly expressed in mast cells, antigen-presenting cells, and Th-2 cells. HPGDS converts PGH2 into PGD2, a mediator thought to play a pivotal role in airway allergy and inflammatory processes. In this letter, we report the discovery of an orally potent and selective inhibitor of HPGDS that reduces the antigen-induced response in allergic sheep.

Ethnic disparities in cervical cancer survival among Texas women.

OBJECTIVE: The aim of this work was to determine whether minority women are more likely to die of cervical cancer. A population-based cohort study was performed using Texas Cancer Registry (TCR) data from 1998 to 2002. METHODS: A total of 5,166 women with cervical cancer were identified during 1998-2002 through the TCR. Measures of socioeconomic status (SES) and urbanization were created using census block group-level data. Multilevel logistic regression was used to calculate the odds of dying from cervical cancer by race, and Cox proportional hazards modeling was used for cervical cancer-specific survival analysis. RESULTS: After adjusting for age, SES, urbanization, stage, cell type, and treatment, Hispanic women were significantly less likely than non-Hispanic White women to die from cervical cancer (adjusted hazard ratio [aHR] = 0.69; 95% CI [confidence interval] = 0.59-0.80), whereas Black women were more likely to die (aHR = 1.26; 95% CI = 1.06-1.50). Black and Hispanic women were more likely to be diagnosed at a later stage than White women. Black women were significantly less likely to receive surgery among those diagnosed with localized disease (p = 0.001) relative to both White and Hispanic women. CONCLUSIONS: Relative to non-Hispanic White women, Black women were more likely to die of cervical cancer while Hispanic women were less likely to die; these survival differences were not explained by SES, urbanization, age, cell type, stage at diagnosis, or treatment.

Understanding the burden of human papillomavirus-associated anal cancers in the US.

BACKGROUND: Anal cancer is an uncommon malignancy in the US; up to 93% of anal cancers are associated with human papillomavirus. METHODS: Cases diagnosed between 1998 and 2003 from 39 population-based cancer registries were analyzed. The following anal cancer histologies were included in the analysis: squamous cell, adenocarcinoma, and small cell/neuroendocrine carcinomas. Incidence rates were age-adjusted to the 2000 US standard population. RESULTS: From 1998 through 2003, the annual age-adjusted invasive anal cancer incidence rate was 1.5 per 100,000 persons. Squamous cell carcinoma (SCC) was the most common histology overall, accounting for 18,105 of 21,395 (84.6%) cases of anal cancer. Women had a higher rate of SCC (1.5 per 100,000) than men (1.0). Whites and blacks had the highest incidence rate (1.3), whereas Asians/Pacific Islanders (API) had the lowest rate (0.3). Incidence rates of anal SCC increased 2.6% per year on average. The majority of SCC cases were diagnosed at the in situ or localized stage (58.1%). API were more likely to be diagnosed with regional or distant stage disease than were other racial/ethnic groups (27.5% and 11.8%, respectively). Males had lower 5-year relative survival than females for all stages of disease. CONCLUSIONS: Rates of anal SCC varied by sex, race, and ethnicity. A higher proportion of API were diagnosed at regional/distant stage. Men had lower 5-year survival rates than women. Continued surveillance and additional research are needed to assess the potential impact of the HPV vaccine on the anal cancer burden in the US.