Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific ...insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993-97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999-2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.
The purpose of this study was to identify germline single nucleotide polymorphisms (SNPs) that optimally predict radiation-associated contralateral breast cancer (RCBC) and to provide new biological ...insights into the carcinogenic process. Fifty-two women with contralateral breast cancer and 153 women with unilateral breast cancer were identified within the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study who were at increased risk of RCBC because they were ≤ 40 years of age at first diagnosis of breast cancer and received a scatter radiation dose > 1 Gy to the contralateral breast. A previously reported algorithm, preconditioned random forest regression, was applied to predict the risk of developing RCBC. The resulting model produced an area under the curve (AUC) of 0.62 (p = 0.04) on hold-out validation data. The biological analysis identified the cyclic AMP-mediated signaling and Ephrin-A as significant biological correlates, which were previously shown to influence cell survival after radiation in an ATM-dependent manner. The key connected genes and proteins that are identified in this analysis were previously identified as relevant to breast cancer, radiation response, or both. In summary, machine learning/bioinformatics methods applied to genome-wide genotyping data have great potential to reveal plausible biological correlates associated with the risk of RCBC.
Next Generation Sequencing (NGS) technologies are used to detect somatic mutations in tumors and study germ line variation. Most NGS studies use DNA isolated from whole blood or fresh frozen tissue. ...However, formalin-fixed paraffin-embedded (FFPE) tissues are one of the most widely available clinical specimens. Their potential utility as a source of DNA for NGS would greatly enhance population-based cancer studies. While preliminary studies suggest FFPE tissue may be used for NGS, the feasibility of using archived FFPE specimens in population based studies and the effect of storage time on these specimens needs to be determined. We conducted a study to determine whether DNA in archived FFPE high-grade ovarian serous adenocarcinomas from Surveillance, Epidemiology and End Results (SEER) registries Residual Tissue Repositories (RTR) was present in sufficient quantity and quality for NGS assays. Fifty-nine FFPE tissues, stored from 3 to 32 years, were obtained from three SEER RTR sites. DNA was extracted, quantified, quality assessed, and subjected to whole exome sequencing (WES). Following DNA extraction, 58 of 59 specimens (98%) yielded DNA and moved on to the library generation step followed by WES. Specimens stored for longer periods of time had significantly lower coverage of the target region (6% lower per 10 years, 95% CI: 3-10%) and lower average read depth (40x lower per 10 years, 95% CI: 18-60), although sufficient quality and quantity of WES data was obtained for data mining. Overall, 90% (53/59) of specimens provided usable NGS data regardless of storage time. This feasibility study demonstrates FFPE specimens acquired from SEER registries after varying lengths of storage time and under varying storage conditions are a promising source of DNA for NGS.
To examine the impact of cancer on work and education in a sample of adolescent and young adult (AYA) patients with cancer.
By using the Adolescent and Young Adult Health Outcomes and Patient ...Experience Study (AYA HOPE)-a cohort of 463 recently diagnosed patients age 15 to 39 years with germ cell cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, sarcoma, and acute lymphocytic leukemia from participating Surveillance, Epidemiology, and End Results (SEER) cancer registries-we evaluated factors associated with return to work/school after cancer diagnosis, a belief that cancer had a negative impact on plans for work/school, and reported problems with work/school after diagnosis by using descriptive statistics, χ(2) tests, and multivariate logistic regression.
More than 72% (282 of 388) of patients working or in school full-time before diagnosis had returned to full-time work or school 15 to 35 months postdiagnosis compared with 34% (14 of 41) of previously part-time workers/students, 7% (one of 14) of homemakers, and 25% (five of 20) of unemployed/disabled patients (P < .001). Among full-time workers/students before diagnosis, patients who were uninsured (odds ratio OR, 0.21; 95% CI, 0.07 to 0.67; no insurance v employer-/school-sponsored insurance) or quit working directly after diagnosis (OR, 0.15; 95% CI, 0.06 to 0.37; quit v no change) were least likely to return. Very intensive cancer treatment and quitting work/school were associated with a belief that cancer negatively influenced plans for work/school. Finally, more than 50% of full-time workers/students reported problems with work/studies after diagnosis.
Although most AYA patients with cancer return to work after cancer, treatment intensity, not having insurance, and quitting work/school directly after diagnosis can influence work/educational outcomes. Future research should investigate underlying causes for these differences and best practices for effective transition of these cancer survivors to the workplace/school after treatment.
Lung transplant recipients have an increased risk of lung cancer that is poorly understood. Prior studies are largely descriptive and single‐center, and have not examined risk factors or outcomes in ...this population. This registry‐linkage study utilized matched transplant and cancer registry data from 17 US states/regions during 1987‐2012. We used standardized incidence ratios (SIRs) to compare incidence with the general population, Poisson models to identify lung cancer risk factors, and Cox models to compare survival after diagnosis. Lung cancer risk was increased among lung recipients (SIR 4.8, 95% confidence interval CI 4.1‐5.5). Those with single lung transplant had 13‐fold (95% CI 11‐15) increased risk in the native lung. Native lung cancer risk factors included age, prior smoking, time since transplant, and idiopathic pulmonary fibrosis. Compared with cases in the general population, lung cancers in recipients were more frequently localized stage (P = .02) and treated surgically (P = .05). However, recipients had higher all‐cause (adjusted hazard ratio 1.90, 95% CI 1.52‐2.37) and cancer‐specific mortality (adjusted hazard ratio 1.67, 95% CI 1.28‐2.18). In conclusion, lung cancer risk is increased after lung transplant, especially in the native lung of single lung recipients. Traditional risk factors are associated with lung cancer in these patients. Lung cancer survival is worse among lung recipients despite earlier diagnosis.
In this registry‐linkage study using matched transplant and cancer registry data, the authors compare lung cancer risk, risk factors, stage, and survival between lung transplant recipients and the general population, demonstrating an elevated risk of lung cancer and poor survival among transplant recipients.
Background: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using ...population-based data from throughout the United States.
Materials and Methods: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians contacted for verification. Application of the Children's Oncology Group (COG)'s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making provided insight to community-based treatment patterns. Kaplan-Meier survival analyses, based on 5-years of follow-up, were also performed.
Results: 76% of the 250 patients were enrolled on an open/active clinical trial. All low-risk patients received surgery. Most intermediate-risk patients (81%) received a chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, myeloablative chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. 21% patients had died at the end of the maximum 60-month follow-up period. The 5-year estimated survival rates were lower for patients diagnosed with stage 4 disease, unfavorable DNA ploidy, MYCN gene amplification or classified as high-risk.
Conclusion: Most neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy received by these patients.
Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed human immunodeficiency virus–infected people. Using data from the US transplant registry linked with 17 ...cancer registries (1987‐2014), we studied PCNSL and systemic non‐Hodgkin lymphoma (NHL) in 288 029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio = 65.1; N = 168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N = 2043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio aIRR = 0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR = 2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non‐Hispanic whites (aIRR = 2.09); after induction immunosuppression with alemtuzumab (aIRR = 3.12), monoclonal antibodies (aIRR = 1.83), or polyclonal antibodies (aIRR = 2.03); in recipients who were Epstein‐Barr virus–seronegative at the time of transplant and at risk of primary infection (aIRR = 1.95); and within the first 1.5 years after transplant. Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio aHR = 11.79) or graft failure/retransplantation (aHR = 3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR = 1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis.
In a large population‐based cohort study of solid organ transplant recipients, risk of primary central nervous system lymphoma was substantially elevated, especially within the first 1.5 years after transplant and in recipients who were seronegative for Epstein–Barr virus infection, and the diagnosis was associated with higher mortality than other systemic non‐Hodgkin lymphomas.
Up to one-third of women with ovarian cancer in the United States do not receive surgical care from a gynecologic oncologist specialist despite guideline recommendations. We aim to investigate the ...impact of rurality on receiving surgical care from a specialist, referral to a specialist, and specialist surgery after referral, and the consequences of specialist care.
We utilized a retrospective cohort created through an extension of standard cancer surveillance in three Midwestern states. Multivariable adjusted logistic regression was utilized to assess gynecologic oncologist treatment of women 18–89 years old, who were diagnosed with primary, histologically confirmed, malignant ovarian cancer in 2010–2012 in Kansas, Missouri and Iowa by rurality.
Rural women were significantly less likely to receive surgical care from a gynecologic oncologist specialist (adjusted odds ratio (OR) 0.37, 95% confidence interval (CI) 0.24–0.58) and referral to a specialist (OR 0.37, 95% CI 0.23–0.59) compared to urban women. There was no significant difference in specialist surgery after a referral (OR 0.56, 95% CI 0.26–1.20). Rural women treated surgically by a gynecologic oncologist versus non-specialist were more likely to receive cytoreduction and more complete tumor removal to ≤1 cm.
There is a large rural-urban difference in receipt of ovarian cancer surgery from a gynecologic oncologist specialist (versus a non-specialist). Disparities in referral rates contribute to the rural-urban difference. Further research will help define the causes of referral disparities, as well as promising strategies to address them.
•Rural ovarian cancer patients are 63% less likely to receive a referral to a gynecologic oncologist for surgery•Rural ovarian cancer patients are significantly less likely to receive surgery from a gynecologic oncologist•After a surgical referral, rural ovarian cancer patients are just as likely to receive surgery from a specialist•Specialist-provided surgery increases receipt of cytoreduction and complete tumor removal for rural ovarian cancer patients•Rural women (versus urban) who receive surgery from a gynecologic oncologist travel farther to surgical care
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