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.

Rheumatology laboratory tests are often inappropriately ordered in situations for which they are of low diagnostic utility. We surveyed pediatricians to investigate reasons for ordering these tests. The response rate was 15.3% (93/609). The most commonly ordered tests were antinuclear antibody (ANA), anti-double-stranded DNA (dsDNA) antibody, and rheumatoid factor (RF). Of the 89% (83/93) who ordered an ANA, 86% ordered it for correct/possibly correct reasons; of the 73% (68/93) who ordered RF, 80% did so for correct/possibly correct reasons; and among the 59% (54/92) who had ordered anti-dsDNA antibody, 34% ordered it for correct reasons. A positive relationship was seen between years since residency completion and correct use of ANA. However, positive associations were not seen between measures of pediatric rheumatology experience and correct use of other tests. Interventions are needed to improve pediatricians' utilization of rheumatology tests.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in many countries, with metastatic disease responsible for most patient deaths. This study compares the prevalence of metastatic OS at diagnosis across countries to inform the critical question of whether diagnostic delay or tumor biology drives metastases development prior to diagnosis. PROCEDURE: A literature search of the PubMed database was conducted to compare the prevalence of metastatic disease at the time of OS diagnosis between countries. A pooled prevalence with 95% confidence intervals was calculated for each study meeting inclusion criteria. Studies were grouped for analysis based on human development index (HDI) scores. RESULTS: Our analysis found an 18% (95% confidence interval [CI]: 15%, 20%) average global pooled proportion of metastasis at OS diagnosis. The average prevalence of metastasis at diagnosis increased as HDI groupings decreased, with very high HDI, high HDI, and medium/low HDI groups found to be 15% (95% CI: 13%, 17%), 20% (95% CI: 14%, 28%), and 31% (95% CI: 15%, 52%), respectively. CONCLUSIONS: Our evidence suggests there is a biological baseline for metastatic OS at diagnosis, which is observed in countries with very high HDI. In countries with medium/low HDI, where there are more barriers to accessing healthcare, the higher prevalence of metastasis may result from treatment delay or an artificial prevalence inflation due to patients with less severe symptoms not presenting to clinic. Additional research in countries with medium/low HDI may reveal that earlier detection and treatment could improve patient outcomes in those countries.

Pathogenic germline variation in TP53, usually accompanied by familial Li-Fraumeni syndrome (LFS), is known to underly a small proportion of pediatric osteosarcoma (OS). However, the extent to which de novo mutations and rare but mildly deleterious variation in TP53 are found in the genomes of OS patients is only now coming into focus with next-generation sequencing. We recruited 285 patients with OS diagnosed at <20 years of age from North American Children's Oncology Group institutions between December, 2007 and March, 2010. Oragene saliva collection kits (DNA Genotek, Ottawa, Canada) or buccal swabs for DNA extraction were collected from patients and their parents, resulting in 229 complete triads and 59 dyads. From these, 95 triads were selected for whole exome sequencing (WES) based on the availability of both patient and parent samples and sufficient DNA mass. Libraries were created using the Agilent SureSelect All Exon V5+UTRs kit and were sequenced using a HiSeq 2000 that generated 100bp paired end reads with an average insert size of 188.8bp. We implemented the best practices as delineated in the GATK pipeline, including using BWA-MEM for alignment, GATK for quality recalibration and indel realignment, and GATK HaplotypeCaller for genotyping. On average, 35.0 million reads were delivered per sample, and the average read depth was 36.4x coverage. The average proportion of TP53 exons covered at 20x coverage was 76.2% (compared to 78.7% for all genes). Exons 1 and 9 were the only exons with poor coverage (mean coverage <20x). All putative TP53 variants were verified via Sanger sequencing; only verified variants are reported hereafter. Sequence variants were annotated using SNPEFF and ANNOVAR. Five patients exhibited rare, synonymous variation in exons 4 (Pro36Pro, 2 patients) and 6 (Arg213Arg, 3 patients). One patient exhibited rare, non-synonymous variation in exon 4 (Pro47Ser); this variant has a frequency of 0.005 across all populations in 1000 Genomes data and was predicted to be deleterious in 2 of 8 functional prediction algorithms. An additional two patients exhibited rare, non-synonymous variation in exons 7 (Cys238Tyr) and 8 (Gly279Glu). Neither variant was detected in parents or reported in 1000 Genomes data, and both were predicted to be deleterious by all functional prediction algorithms. The prevalence of pathogenic TP53 variation in our data (3/95 or 3.2%) is roughly similar to that reported previously, but importantly 2 of the 3 rare, non-synonymous variants were de novo. These results underscore the contribution of new mutations to OS risk and suggest that genetic counseling and TP53 mutation testing should be offered to patients even in the absence of a family history suggestive of LFS. This research was funded by NIH R01CA122371 and grants from the Hyundai Hope on Wheels foundation and the Zach Sobiech Osteosarcoma Fund of the Children's Cancer Research Fund, Minneapolis, MN. Citation Format: Logan Spector, Ian Lock, John Lane, Aaron Sarver, Mark Krailo, Rajaram Nagarajan, Nathan Pankratz. De novo and transmitted germline TP53 variation in pediatric osteosarcoma: A report from the Children's Oncology Group. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A37.

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.

BACKGROUND The long-term outcomes of patients undergoing interventions for congenital heart disease (CHD) remain largely unknown. We linked the Pediatric Cardiac Care Consortium (PCCC) with the National Death Index (NDI) and the United Network for Organ Sharing Dataset (UNOS) registries to study mortality and transplant occurring up to 32 years postintervention. The objective of the current analysis was to determine the sensitivity of this linkage in identifying patients who are known to have died or undergone heart transplant. METHODS AND RESULTS We used direct identifiers from 59 324 subjects registered in the PCCC between 1982 and 2003 to test for completeness of case ascertainment of subjects with known vital and heart transplant status by linkage with the NDI and UNOS registries. Of the 4612 in-hospital deaths, 3873 were identified by the NDI as "true" matches for a sensitivity of 84.0% (95% CI, 82.9-85.0). There was no difference in sensitivity across 25 congenital cardiovascular conditions after adjustment for age, sex, race, presence of first name, death year, and residence at death. Of 455 known heart transplants in the PCCC, there were 408 matches in the UNOS registry, for a sensitivity of 89.7% (95% CI, 86.9-92.3). An additional 4851 deaths and 363 transplants that occurred outside the PCCC were identified through 2014. CONCLUSIONS The linkage of the PCCC with the NDI and UNOS national registries is feasible with a satisfactory sensitivity. This linkage provides a conservative estimate of the long-term death and heart transplant events in this cohort.

We read with interest the article by Pasquali et al1 exploring opportunities and challenges toward an integrated data network for congenital heart disease research. We fully agree with the authors’ conclusion that there is a need for additional integration and collaboration to understand and improve the outcomes for patients with congenital heart disease. A particular gap that needs to be addressed is the lack of long-term and longitudinal outcomes for this population. To achieve this goal, it is important to …

OBJECTIVE: To evaluate the risk of maternal morbidity due to IVF, plurality, and maternal age. DESIGN: Longitudinal case-control cohort study MATERIALS AND METHODS: IVF cycles from the Society for Assisted Reproductive Technology Clinic Online Reporting System were linked to birth certificates of singletons and twins in CA (2004-09), and PA, MI, NY, TX (2004-10) (IVF births); a 10:1 sample of non-IVF births were controls. Maternal morbidity was identified from six items on the birth certificate (see below). Using logistic regression, the risk of each morbidity was modeled by maternal age, IVF versus non-IVF conception, and plurality (twin versus singleton), separately for each mode of delivery. Parity was included in the model for perineal laceration. RESULTS: The study population included 53,053 IVF births (37,193 singletons and 15,860 twin births) and 576,880 non-IVF control births (567,856 singletons and 9,024 twin births). Regardless of mode of delivery, older maternal age was associated with an increased risk of unplanned hysterectomy and unplanned operations; twin pregnancy with blood transfusion, admission to intensive care, and unplanned operations; and IVF pregnancy with blood transfusion. Women with vaginal IVF births were at increased risk for unplanned hysterectomy, unplanned operations, and 3rd or 4th degree perineal lacerations. Cesarean twin births were at increased risk of unplanned hysterectomy. CONCLUSIONS: The risks of maternal morbidity at delivery are increased with IVF, twin pregnancy, and older maternal age. (Table Presented).

BackgroundRhabdomyosarcoma (RMS) is a rare, highly malignant tumor\narising from primitive mesenchymal cells that differentiate into\nskeletal muscle. Relatively little is known about RMS susceptibility.\nBased on growing evidence regarding the role of early immunologic\nchallenges on RMS development, we evaluated the role of infections and\nimmunizations on this clinically significant pediatric malignancy.\nProcedureRMS cases (n = 322) were enrolled from the third trial\ncoordinated by the Intergroup Rhabdomyosarcoma Study Group.\nPopulation-based controls (n = 322) were pair matched to cases on race,\nsex, and age. The following immunizations were assessed: diphtheria,\npertussis, and tetanus (DPT); measles, mumps, and rubella; and oral\npolio vaccine. We also evaluated if immunizations were complete versus\nincomplete. We examined selected infections including chickenpox, mumps,\npneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis,\nand lung infections. Conditional logistic regression models were used to\ncalculate an odds ratio (OR) and 95% confidence interval (CI) for each\nexposure, adjusted for maternal education and total annual income.\nResultsIncomplete immunization schedules (OR= 5.30, 95% CI: 2.47-11.33)\nand incomplete DPT immunization (OR = 1.56, 95% CI: 1.06-2.29) were\npositively associated with childhood RMS. However, infections did not\nappear to be associated with childhood RMS.\nConclusionsThis is the largest study of RMS to date demonstrating a\npossible protective effect of immunizations against the development of\nchildhood RMS. Further studies are needed to validate our findings. Our\nfindings add to the growing body of literature, suggesting a protective\nrole of routine vaccinations in childhood cancer and specifically in\nchildhood RMS. (C) 2016 Wiley Periodicals, Inc.

Background: Coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) are rare in children (<18 years). We report indications and outcomes of CABG or PCI from a large North American registry of pediatric cardiac centers. Methods: Cohort study from the Pediatric Cardiac Care Consortium (PCCC) for CABG or PCI between 1982 and 2007. Data included age at time of procedure, primary diagnosis, indication, and in-hospital mortality. Long term outcomes were assessed using PCCC follow up data supplemented by data from the United Network for Organ Sharing (UNOS) and the National Death Index (NDI) for a subgroup with adequate identifiers (n=65). Results: We identified 110 coronary revascularization procedures: 19 were performed in infants (CABG 18, PCI 1) and 91 in children (CABG 75, PCI 16). The majority of patients had surgical heart diseases (n=80) including congenital coronary artery abnormalities (n=33), history of arterial switch operation (n=20) or operation at risk for coronary artery injury (n=24). There were 14 in-hospital deaths. Follow-up using the UNOS and NDI identified 10 transplants (OHT) and 10 deaths respectively. The Kaplan Meier plot of the transplant free survival for the cohort submitted to the UNOS and NDI is presented in the Figure with 10-year transplant free survival of 69% (95% CI: 58%- 81%). Conclusions: Coronary revascularization procedures can be performed in children for a variety of indications with acceptable mid-term transplant-free survival.

Background: With today's advancements in surgical or transcatheter interventions about 90% of infants with congenital heart diseases (CHD) are expected to reach adulthood. However, the long term altered history of patients surviving interventions for CHD remains largely unknown. We aim to study mortality patterns in the cohort registered in the Pediatric Cardiac Care Consortium (PCCC) after undergoing interventions for CHD between 1982 and 2003. The PCCC is the longest registry for pediatric cardiac interventions in the world containing data from surgical and transcatheter procedures from 27 U.S. states. Methods: We linked the PCCC dataset with the National Death Index (NDI) using direct identifiers to determine vital status of individuals with repaired or palliated CHD. The identifiers included first name, middle name, last name, day, month and year of birth, state residence at birth and sex. A total of 59,324 subjects registered in the PCCC as having undergone an intervention for CHD up to April 2003 (date of implementation of HIPAA rules) had sufficient identifiers and were submitted for linkage with the NDI. This number includes also 4,655 inhospital deaths recorded in the PCCC registry. After linking with the NDI, these records are assigned by NDI a probabilistic score based on the NDI algorithm and are identified as true or false matches. We tested for completeness of case ascertainment of subjects with known vital status based on their last admission in a PCCC center. Results and Conclusions: Of the 4,655 known deaths submitted to the NDI, 3,906 were identified as “true” matches, 381 as undetermined matches and 368 deaths had no match. Based on these numbers the sensitivity of the PCCC-NDI match is within the range of 82.8% to 85.0% [95% confidence interval]. There was no difference in sensitivity across 48 congenital cardiovascular conditions after adjustment for age, sex, year and state of death. An additional 3,722 deaths were identified through 12/31/2012 that occurred outside the PCCC. These events provide a conservative estimate of deaths that forms the basis for estimating the long term survival of this cohort.

Background: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). Interpretation: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism. Funding: National Cancer Institute.

Certain mitochondrial haplotypes (mthaps) are associated with disease, possibly through differences in oxidative phosphorylation and/or immunosurveillance. We explored whether mthaps are associated with allogeneic hematopoietic cell transplantation (HCT) outcomes. Recipient (n= 437) and donor (n= 327) DNA were genotyped for common European mthaps (H, J, U, T, Z, K, V, X, I, W, and K2). HCT outcomes for mthap matched siblings (n= 198), all recipients, and all donors were modeled using relative risks (RR) and 95% confidence intervals and compared with mthap H, the most common mitochondrial haplotypes. Siblings with I and V were significantly more likely to die within 5 years (RR= 3.0; 95% confidence interval [CI], 1.2 to 7.9; and RR= 4.6; 95% CI, 1.8 to 12.3, respectively). W siblings experienced higher acute graft-versus-host disease (GVHD) grades II to IV events (RR= 2.1; 95% CI, 1.1 to 2.4) with no events for those with K or K2. Similar results were observed for all recipients combined, although J recipients experienced lower GVHD and higher relapse. Patients with I donors had a 2.7-fold (1.2 to 6.2) increased risk of death in 5 years, whereas few patients with K2 or W donors died. No patients with K2 donors and few patients with U donors relapsed. Mthap may be an important consideration in HCT outcomes, although validation and functional studies are needed. If confirmed, it may be feasible to select donors based on mthap to increase positive or decrease negative outcomes.

BACKGROUND: Children with Down syndrome have unique immune profiles and increased leukemia susceptibility.\n\nMETHODS: Mothers of 158 children with Down syndrome diagnosed with acute leukemia at 0 to 19 years in 1997 to 2002 and 173 children with Down syndrome but no leukemia were interviewed. Associations were evaluated via multivariable unconditional logistic regression.\n\nRESULTS: No associations were detected for asthma, eczema, allergies, or hypothyroidism. Diabetes mellitus associated with leukemia (OR = 9.23; 95% confidence interval 2.33-36.59); however, most instances occurred concurrent with or after the leukemia diagnosis.\n\nCONCLUSIONS AND IMPACT: Children with Down syndrome who develop leukemia have increased diabetes risk, likely due to treatment and underlying susceptibility factors.

OBJECTIVE\nTo evaluate the risk of cancer after assisted reproductive technology (ART) therapy. \n\nDESIGN\nLongitudinal cohort study. \n\nSETTING\nNot applicable. \n\nPATIENT(S)\nNew 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). \n\nINTERVENTION(S)\nNone. \n\nMAIN OUTCOME MEASURE(S)\nDiagnosis 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. \n\nRESULT(S)\nAmong 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. \n\nCONCLUSION(S)\nWomen 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.

Genetic syndromes and pediatric cancers are rare, so instances of co-occurrence raise the question of whether the two conditions may be etiologically linked. Clear examples of causal association can be found in the cancer predisposition syndromes. This report contains the results of a systematic literature search using Ovid Medline for co- occurrence of genetic syndromes with 23 types of pediatric cancer. The results reflect known associations as well as many reports of infrequently observed co-occurrences. This compilation may suggest previously overlooked patterns, and the information could be used to identify gene pathways critical in the development of childhood cancers. Pediatr Blood Cancer 2015;62:2071–2075.