Patient characteristics associated with definitive diagnosis of metastatic pancreatic cancer in those initially diagnosed with cancer of unknown primary.

Cancer of unknown primary (CUP) and pancreatic cancer (PC) are malignancies associated with poor prognosis. CUP is the fourth most common cause of cancer mortality in the US, and median survival time is 3-4 months. PC is the third most common cause of cancer mortality in the US, and median survival time for patients with stage 3 or 4 PC is 2-3 months. The present study aimed to understand the patient characteristics of those initially misdiagnosed with CUP who ultimately received a diagnosis of PC. The present study used 2010-2015 Surveillance, Epidemiology, and End Results-Medicare data, a US population-based cancer registry linked to Medicare health insurance claims. Odds ratios (ORs) and 95% confidence intervals were calculated using two binary logistic regression models to compare the characteristics of patients who received definitive diagnosis between the CUP-PC group (those with an initial diagnosis of CUP who eventually received a stage 3 or 4 PC diagnosis) and the PC group (those diagnosed with stage 3 or 4 PC only). Approximately 26% of patients who received a definitive diagnosis of metastatic PC started with an initial diagnosis of CUP (n=17,565). The odds of definitive PC diagnosis in patients with CUP were lower for those with a comorbidity score of 0 [OR, 0.85 (95% CI: 0.79, 0.91)] and epithelial/unspecified histology [OR, 0.76 (95% CI: 0.71, 0.82)]. The odds of definitive PC diagnosis in patients with CUP were higher for patients of other race [OR, 1.27 (95% CI: 1.13, 1.43)] compared with white patients. Definitive diagnosis of PC in patients with CUP was lower in patients who were older with fewer or no comorbidities and unspecified histology. The complexity of CUP diagnosis and patient performance status may influence delays in diagnosis to a known primary site.

Patient Characteristics Associated with Definitive Diagnosis of Metastatic Pancreatic Cancer in Those Initially Diagnosed with Cancer of Unknown Primary.

Purpose: Cancer of unknown primary (CUP) is the fourth most common cause of cancer mortality in the U.S. Median survival after CUP diagnosis is 3-4 months. As CUP and metastatic pancreatic cancer (PC) are comparable in prevalence and survival, PC diagnosis is a useful endpoint to assess patient characteristics associated with definitive diagnosis in older patients who initially present with CUP. Methods: This study used 2010-2015 SEER-Medicare data. Logistic regression models compared patient characteristics who received definitive diagnosis in two subsets: CUP-PC and PC only. Results: Approximately 26% of patients who received a definitive diagnosis of metastatic pancreatic cancer started with an initial diagnosis of CUP (n=17,565). The odds of definitive diagnosis in CUP-PC were lower for those with a comorbidity score of 0 (OR 0.85 [0.79, 0.91]) and epithelial/unspecified histology (OR 0.76 [0.71, 0.82]). The odds of definitive diagnosis in CUP-PC were higher for patients of Other race (OR 1.27 [1.13, 1.43]) compared to White patients. Conclusion: Definitive diagnosis of CUP-PC was favorable in patients in the Other race category with fewer or no comorbidities. Unfavorable characteristics included older patients and those with epithelial/unspecified histology. Future studies will focus on patterns of care and survival in patients with CUP-PC.

Systematic review of the CUP trials characteristics and perspectives for next-generation studies.

BACKGROUND: Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic research over the previous five years. Based on this evaluation, recommendations for clinical trial designs are made to improve the impact of CUP research on patients. METHODS: Published and ongoing research were evaluated. PubMed was searched from January 1, 2015, to November 1, 2021. The start date of 2015 was chosen to identify research published after ESMO issued new diagnostic and therapeutic guidelines. The US National Library of Medicine indexed ongoing clinical trials. FINDINGS: Of the 244 CUP studies indexed in PubMed, 11.9% were prospective studies, and 4.9% were clinical trials. The review protocol deemed 65 publications eligible for full-text review. Eleven studies evaluating therapeutic regimens were retained. The two prospective studies and non-randomized trials showed promising outcomes for site-specific treatments. Randomized clinical trials were less promising; however, the trials had recruitment challenges resulting in biased accrual and the inability to keep pace with advancing diagnostics and therapeutics. Most of the 35 ongoing studies were phase II single-arm trials assessing immune checkpoint inhibitors (ICI) or site-specific therapies among CUP patients with suspected favorable prognoses. CONCLUSION: Our evaluation suggests two prospective clinical trial designs that addressed recent study design and recruitment challenges. A visionary approach uses a multi-arm, multistage randomized trial to address rapid advancements in diagnosis and therapy. A pragmatic approach utilizes a single-arm trial with historical controls to overcome comparison group and recruitment challenges.

Optimizing NK-92 serial killers: gamma irradiation, CD95/Fas-ligation, and NK or LAK attack limit cytotoxic efficacy.

BACKGROUND: The NK cell line NK-92 and its genetically modified variants are receiving attention as immunotherapies to treat a range of malignancies. However, since NK-92 cells are themselves tumors, they require irradiation prior to transfer and are potentially susceptible to attack by patients' immune systems. Here, we investigated NK-92 cell-mediated serial killing for the effects of gamma-irradiation and ligation of the death receptor Fas (CD95), and NK-92 cell susceptibility to attack by activated primary blood NK cells. METHODS: To evaluate serial killing, we used 51Cr-release assays with low NK-92 effector cell to target Raji, Daudi or K562 tumor cell (E:T) ratios to determine killing frequencies at 2-, 4-, 6-, and 8-h. RESULTS: NK-92 cells were able to kill up to 14 Raji cells per NK-92 cell in 8 h. NK-92 cells retained high cytotoxic activity immediately after irradiation with 10 Gy but the cells surviving irradiation lost > 50% activity 1 day after irradiation. Despite high expression of CD95, NK-92 cells maintained their viability following overnight Fas/CD95-ligation but lost some cytotoxic activity. However, 1 day after irradiation, NK-92 cells were more susceptible to Fas ligation, resulting in decreased cytotoxic activity of the cells surviving irradiation. Irradiated NK-92 cells were also susceptible to killing by both unstimulated and IL-2 activated primary NK cells (LAK). In contrast, non-irradiated NK-92 cells were more resistant to attack by NK and LAK cells. CONCLUSIONS: Irradiation is deleterious to both the survival and cytotoxicity mediated by NK-92 cells and renders the NK-92 cells susceptible to Fas-initiated death and death initiated by primary blood NK cells. Therefore, replacement of irradiation as an antiproliferative pretreatment and genetic deletion of Fas and/or NK activation ligands from adoptively transferred cell lines are indicated as new approaches to increase therapeutic efficacy.

The outcome of patients with serous papillary peritoneal cancer, fallopian tube cancer, and epithelial ovarian cancer by treatment eras: 27 years data from the SEER registry.

AIM: To determine the differential effect of the treatment periods on the survival of patients with stage IV serous papillary peritoneal carcinoma (SPPC), fallopian tube cancers, and epithelial ovarian cancers (EOC). METHODS: This was an exploratory, population-based observational study of all patients with stage IV SPPC, fallopian tube cancers, and EOC collected from the SEER Research Data 1973-2017. The study period was divided into three time-periods: platinum combinations before the taxane era (1990-1995), platinum plus taxane chemotherapy era (1996-2013), and bevacizumab era (2014-2017). RESULTS: A total of 9828 patients were eligible for analyses: SPPC (3898 patients; 39.7%), fallopian tube cancers (1290 patients; 13.1%) and EOC (4640 patients, 47.2%). In the 1990-1995 era, the 3-year cause-specific survival was 40% for SPPC, 53% for fallopian tube cancers, and 40% for POC. In the following era 1993-2013, the 3-year cause-specific survival increased to 55% for SPPC, 74% for fallopian tube cancers, and 45% for POC. The last era 2014-2017 showed a 3-year cause-specific survival of 64%, 67%, and 45% for patients with SPPC, fallopian tube cancers, and POC, respectively. The differences in cause-specific survival were statistically significant for patients with SPPC (p=0.004). Multivariable analysis showed that the treatment eras and age at diagnosis were associated with cause-specific survival. CONCLUSION: The results of this study are hypothesis-generating and cannot be considered conclusive given the inherent limitations of registry analysis. Subgroup analyses of the phase III randomized controlled trials, by tumor subset (EOC, fallopian tube cancer, and SPPC) would shed more light on the differential effects of novel therapies.

Natural Killer (NK) Cell Expression of CD2 as a Predictor of Serial Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC).

NK cell ADCC supports monoclonal antibody anti-tumor therapies. We investigated serial ADCC and whether it could be predicted by NK phenotypes, including expression of CD16A, CD2 and perforin. CD16A, the NK receptor for antibodies, has AA158 valine or phenylalanine variants with different affinities for IgG. CD2, a costimulatory protein, associates with CD16A and can augment CD16A-signaling. Pore-forming perforin is essential for rapid NK-mediated killing. NK cells were monitored for their ADCC serial killing frequency (KF). KF is the average number of target cells killed per cell by a cytotoxic cell population. KF comparisons were made at 1:4 CD16pos NK effector:target ratios. ADCC was toward Daudi cells labeled with 51Cr and obinutuzumab anti-CD20 antibody. CD16A genotypes were determined by DNA sequencing. CD2, CD16A, and perforin expression was monitored by flow cytometry. Serial killing KFs varied two-fold among 24 donors and were independent of CD16A genotypes and perforin levels. However, high percentages of CD2pos of the CD16Apos NK cells and high levels of CD16A were associated with high KFs. ROC analysis indicated that the %CD2pos of CD16Apos NK cells can predict KFs. In conclusion, the extent of serial ADCC varies significantly among donors and appears predictable by the CD2posCD16Apos NK phenotype.

Inclusion of family members without ME/CFS in research studies promotes discovery of biomarkers specific for ME/CFS.

BACKGROUND: The search for a biomarker specific for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been long, arduous and, to date, unsuccessful. Researchers need to consider their expenditures on each new candidate biomarker. In a previous study of antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer lymphocytes, we found lower ADCC for ME/CFS patients vs. unrelated donors but ruled against low ADCC as a biomarker because of similar ADCC for patients vs. their family members without ME/CFS. OBJECTIVE: We applied inclusion of family members without ME/CFS, from families with multiple CFS patients, as a second non-ME/CFS control group in order to re-examine inflammation in ME/CFS. METHOD: Total and CD16A-positive 'non-classical' anti-inflammatory monocytes were monitored. RESULTS: Non-classical monocytes were elevated for patients vs. unrelated healthy donors but these differences were insignificant between patients vs. unaffected family members. CONCLUSIONS: Inclusion of family members ruled against biomarker considerations for the monocytes characterized. These pilot findings for the non-classical monocytes are novel in the field of ME/CFS. We recommend that occupational therapists advocate and explain to family members without ME/CFS the need for the family members' participation as a second set of controls in pilot studies to rapidly eliminate false biomarkers, optimize patient participation, and save researchers' labor.

Cancer of unknown primary: Incidence rates, risk factors and survival among adolescents and young adults.

Cancer of unknown primary (CUP) is a clinical challenge especially when it occurs in adolescents and young adults (AYA), aged 15-39 years, due to the sparse data in this population. The available data has not described the population-based epidemiological features of CUP among AYA. Therefore, we collected patient information from the Surveillance, Epidemiology and End Results (SEER) registry, 1990-2015. Age, gender, ethnic, five pathological classification groups were assessed along with an aggregate level socioeconomic status (SES) index and population density at the county level. Incidence rates, modeled relative risks and survival of AYA patients with CUP were assessed. Among 2,480 AYA patients, 907 met the definition of standard pathology classifications. The majority of AYA patients with CUP had a neuroendocrine, squamous cell and poorly differentiated carcinomas with 0.4 cases per 1,000,000 population. AYA living in areas with the highest SES level had the highest risks of CUP; adjusted relative risks (ARR) of 1.17 (95% CI 1.0-1.4) and 1.99 (95% CI 1.5-2.6), respectively. AYA living in nonmetropolitan areas had a lower risk of CUP (ARR = 0.16; 95% CI 0.1-0.2). The incidence of differentiated neoplasms has been decreasing slower than undifferentiated neoplasms since the early 1990s. The median overall survival (OS) was 11 months (95% CI 9-13 months) with squamous CUP having the longest median OS 16 years (95% CI 3-24 years). In conclusion, this analysis answers several gaps in the knowledge of CUP among AYA and provides a platform to better understand this disease and its management within this group.

Narrative review on serous primary peritoneal carcinoma of unknown primary site: four questions to be answered.

Serous peritoneal papillary carcinoma (SPPC) represents a particular cancer of unknown primary (CUP) entity that arises in the peritoneal surface lining the abdomen and pelvis without a discriminative primary tumor site. In this review, we discuss the validity of SPPC as a distinct entity. Clinically, patients with SPPC are older, have higher parity and later menarche, are more often obese and probably have poorer survival compared to those with primary ovarian cancer. Pathologically, SPPC is more anaplastic and multifocal, unlike primary ovarian cancer which is commonly unifocal. Biologically, it presents a higher expression of proliferative signals and similar cell cycle and DNA repair protein expression. These differences hint towards SPPC and primary ovarian cancer being as a spectrum of disease. Patients with SPPC are traditionally managed similarly to stage III-IV ovarian cancer. The recommended approach integrates aggressive cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, and systemic chemotherapy to remove the macroscopic tumor, eradicate the microscopic residual disease, and control the microscopic metastasis. However, the available evidence lacks proper randomized or prospective studies on SPPC and is limited to retrospective series. The diligent identification of SPPC is warranted to design specific clinical trials that eventually evaluate the impact of the new therapeutics on this distinct entity.

Extent of diagnostic inquiry among a population-based cohort of patients with cancer of unknown primary.

PURPOSE: Current cancer registry data cannot distinguish a justified cancer of unknown primary (CUP) diagnosis, where the patient received a complete diagnostic evaluation that was unable to identify the primary tumor, from potentially misclassified patients, documented as CUP but not based on a complete diagnostic evaluation. This misclassification may skew population-based cancer registry surveillance research used to frame and guide translational CUP research. We identified characteristics of patients who received justified vs. potentially misclassified CUP diagnoses in cancer registry data. METHODS: We developed a conceptual definition of a complete diagnostic evaluation from professional society-recommended guidelines. We translated this definition into procedure codes in the Medicare encounter data. We assessed age, gender, comorbidities, urban or rural residence, income, race, and tumor pathology by receipt of a complete diagnostic evaluation and palliative therapy among 10,575 elderly CUP patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset. We calculated odds ratios and adjusted probabilities using marginal standardization. RESULTS: Only 35% of elderly CUP patients identified in the cancer registry received a complete diagnostic evaluation. After adjustment for age and comorbidities, socioeconomic barriers to a complete diagnostic evaluation persisted: adjusted odds ratio and 95% confidence interval (AOR) for rural vs. urban 0.8(0.8,0.9) and for highest income vs. lowest income 1.2(1.1,1.4). Patients with vague or undocumented tumor pathology in SEER had 80% lower odds of receiving a complete diagnostic evaluation AOR(95%CI)=0.2(0.2,0.2). Although patients with a complete diagnostic evaluation were twice as likely to receive palliative therapy than those without a complete evaluation, AOR(95%CI)=2.0(1.7,2.3), they only had a 46.7% probability of receiving therapy, 95%CI=(44.4,49.1). CONCLUSION: Patients without a complete diagnostic evaluation are not limited to the frail and underserved. For accurate assessment of the CUP burden and disparities in utilization of diagnostic care, we recommend that the SEER definition of CUP include the extent of diagnostic inquiry.

Scope-of-practice laws and expanded health services: the case of underserved women and advanced cervical cancer diagnoses.

BACKGROUND: Underserved women (rural, minority or poor) are disproportionally diagnosed with late-stage cervical cancer, indicative of inadequate access to, and use of, preventative healthcare. The Institute of Medicine (IOM) has proposed that nurse practitioners (NP) can address provider shortages among underserved populations, but to reduce shortages, scope-of-practice laws that restrict the delivery of care, must be revised. We examined the IOM recommendation of NP expanded scope-of-practice laws on reducing the disparity of underserved women diagnosed with late-stage cervical cancer. METHODS: We examined the cohort of 10 673 women diagnosed with cervical cancer between 2010 and 2014 and reported to the Surveillance, Epidemiology and End Results cancer registry. We linked state-level laws regarding NP scope-of-practice to patients with cancer by their state of residence, diagnosis date and law enactment date. Hierarchical regression was used to explore NP full scope-of-practice law's impact on late-stage cancer diagnoses considering the moderating effect of women living in medically underserved areas. We adjusted for known confounders available in this population-based data set. RESULTS: Medically underserved women living in states with laws that restrict NP full scope-of-practice are twofold more likely to be diagnosed with late-stage cancer; adjusted OR and 95% CI (OR 2.08, 95% CI 1.4 to 3.1). These disparities were not observed among underserved women living in areas with NP full scope-of-practice laws (OR 0.95, 95% CI 0.7 to 1.3). CONCLUSIONS: NP full scope-of-practice laws could provide a pragmatic and cost-effective solution to healthcare provider shortages associated with late stage of cervical cancer diagnoses among underserved women.

An improved method to quantify human NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) per IgG FcR-positive NK cell without purification of NK cells.

Natural killer (NK) lymphocyte ADCC supports anti-viral protection and monoclonal antibody (mAb) anti-tumor therapies. To predict in vivo ADCC therapeutic responses of different individuals, measurement of both ADCC cellular lytic capacity and their NK cellular receptor recognition of antibodies on 'target' cells are needed, using clinically available amounts of blood. Twenty ml of blood provides sufficient peripheral blood mononuclear cells (PBMCs) for the new assay for lytic capacity described here and for an antibody EC50 assay for Fc-receptor recognition. For the lytic capacity assay, we employed flow cytometry to quantify the CD16A IgG Fc-receptor positive NK effector cells from PBMCs to avoid loss of NKs during isolation. Targets were 51Cr-labeled Daudi B cells pretreated with excess obinutuzumab type 2 anti-CD20 mAb and washed; remaining free mAb was insufficient to convert B cells in the PBMCs into 'targets'. We calculated: the percentage Daudis killed at a 1:1 ratio of CD16A-positive NK cells to Daudis (CX1:1); lytic slopes; and ADCC50 lytic units. Among 27 donors, we detected wide ranges in CX1:1 (16-73% targets killed) and in lytic slopes. Slope variations prevented application of lytic units. We recommend CX1:1 to compare individuals' ADCC capacity. CX1:1 was similar for purified NK cells vs. PBMCs and independent of CD16A V & F genotypes and antibody EC50s. With high mAb bound onto targets and the high affinity of obinutuzumab Fc for CD16A, CX1:1 measurements discern ADCC lytic capacity rather than antibody recognition. This assay allows ADCC to be quantified without NK cell isolation and avoids distortion associated with lytic units.

A comparison of marginal odds ratio estimators.

Uses of the propensity score to obtain estimates of causal effect have been investigated thoroughly under assumptions of linearity and additivity of exposure effect. When the outcome variable is binary relationships such as collapsibility, valid for the linear model, do not always hold. This article examines uses of the propensity score when both exposure and outcome are binary variables and the parameter of interest is the marginal odds ratio. We review stratification and matching by the propensity score when calculating the Mantel-Haenszel estimator and show that it is consistent for neither the marginal nor conditional odds ratio. We also investigate a marginal odds ratio estimator based on doubly robust estimators and summarize its performance relative to other recently proposed estimators under various conditions, including low exposure prevalence and model misspecification. Finally, we apply all estimators to a case study estimating the effect of Medicare plan type on the quality of care received by African-American breast cancer patients.

How Does Managed Care Improve the Quality of Breast Cancer Care Among Medicare-Insured Minority Women?

PURPOSE: The aim of this study is to investigate if evidence-based clinical guidelines are implemented equitability among ethnic minority breast cancer patients using Medicare Advantage and investigate if presumed advantages of managed care over fee-for-service are greater for minorities than for Whites. METHODS: Data from the Surveillance, Epidemiology, and End Results and Medicare were used to examine 70,755 women over age 65 diagnosed with early stage breast cancer between 2005 and 2009. Implementation of two clinical guidelines was assessed: receipt of radiation therapy after breast conserving surgery and estrogen receptor status documentation. Multilevel logistic regression and inverse propensity weighting controlled for confounding. RESULTS: African Americans are still less likely than Whites to receive radiation therapy after breast-conserving surgery, whether they use Medicare fee-for-service (OR 95 % CI) = 0.90 (0.83, 0.98) or managed care (OR 95 % CI) = 0.87 (0.76, 1.00). Differences between receipt of radiation therapy by insurance plan type was nonexistent. Relative to FFS, the use of managed care improved the odds of having estrogen receptor status documented by 44 % in African Americans, (OR 95 % CI) = 1.44 (1.15, 1.83) and by 42 % in Latina patients (OR 95 % CI) = 1.42 (1.17, 1.78). CONCLUSIONS: Compared to Medicare fee-for-service, ethnic and racial disparities among Medicare Advantage users were reduced. We observed fewer disparities, but not an elimination of disparities, among Medicare Advantage enrollees receiving breast cancer care with an organizational and patient component of care. This suggests managed care may still need to focus on minority patient empowerment and involvement in care.

Latina Women and Cervical Cancer Screening: Decisional Balance and Self-Efficacy.

BACKGROUND: Latina women in the United States have greater cervical cancer mortality rates than non-Latina women because of their low rates of Papanicolau (Pap) smear screening. OBJECTIVES: The purpose of this article is to assess differences in perceived benefits, perceived barriers, and self-efficacy among Latina women to obtain Pap smears using the framework of the Transtheoretical Model. METHODS: A descriptive design with a snowball sample was used. The researchers assessed demographics, three perceived benefits, 12 barriers, and seven self-efficacy measures for 121 Latina women in northern Nevada. FINDINGS: Participants in precontemplation and relapse perceived greater barriers than those in action and maintenance for three items.

Application of the Transtheoretical Model to Cervical Cancer Screening in Latina Women.

This study examined the relationship between the intention to receive Pap tests for cervical cancer screening, as related to the transtheoretical model of behavior change, and self-efficacy, and perceived barriers and benefits among Latina women. A sample of 121 Latina women recruited from a University campus completed validated questionnaires. Over half the participants (62 %) reported engaging in regular cervical screening. The greatest self-efficacy scores were observed among women in the action/maintenance phase, and the least self-efficacy was observed among women in the no-intention phases of behavior change. There was also a gradient in perceived barriers and the stages of change, women in precontemplative/relapse perceived significantly higher barriers than those in contemplation/preparation and action/maintenance. This study identifies a high-risk group of Latina women and demonstrates a need for culturally targeted Pap screening interventions using validated and theoretically driven behavior change interventions focusing on perceived barriers and benefits, and self-efficacy.

Changing incidence of myeloproliferative neoplasms: trends and subgroup risk profiles in the USA, 1973-2011.

PURPOSE: Recent diagnostic and cancer reporting changes influencing myeloproliferative neoplasms (MPNs) encourage the assessment of trends and examination of the recently identified MPN subtypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), across the age continuum by race and ethnicity. METHODS: Surveillance, Epidemiology, and End Results data provided MPN incidence data since 1973 and MPN subtype data since 2001. Joinpoint regression estimated annual percent changes. Poisson regression estimated risk ratios. RESULTS: The 2005 JAK2 V617F discovery and the 2008 WHO diagnostic guideline for the JAK2 V617F mutation coincide with a 31 % increase in ET and a 21 % decrease in PV incidence rates. We found that younger women had a 13-33 % higher ET risk and that women under the age of 34 had a 58 % higher PMF risk, relative to men. Blacks, aged 35-49 with a higher ET risk, also had a 69 % higher PMF risk relative to whites. CONCLUSION: Demographic characteristic of ET and PMF patients may be useful for improving risk prediction and informing clinical screening and treatment strategies. Changing guidelines, new discoveries, and in-depth analysis of a large population-based study have implications for accurately identifying incident cases of MPNs, MPN subgroups, and health resource planning.

Associations between body mass and papillary thyroid cancer stage and tumor size: a population-based study.

PURPOSE: The incidence of large thyroid tumors has increased over the past decades, suggesting that improved diagnosis is not the only driver of increased thyroid cancer incidence. Obesity has recently been implicated as an independent risk factor for thyroid cancer in specific populations. We aimed to investigate whether thyroid tumor size and advanced stage of diagnosis is associated with the obesity epidemic, for the first time, in a US population-based cohort. METHODS: We leveraged existing data and linked 1,077 papillary thyroid cancer patients from the Nevada Central Cancer Registry to the Department of Motor Vehicle dataset. Tumor size and cancer stage were assessed from cancer registry records, and obesity was obtained using height and weight in the Department of Motor Vehicle records and measured by a body mass index greater than 25 kg/m(2). RESULTS: Crude analysis showed obesity as was associated with tumors larger than 2 cm [odds ratio (OR) 1.50, p = 0.0423] and advanced cancer stage (stage III and IV) (OR 1.40, p = 0.0111). After adjusting for confounders, a significant association was still observed between obesity and tumor larger than 2 cm (OR 1.53, p = 0.0339). A marginally significant association was shown between obesity and advanced cancer stage (OR 1.29, p = 0.0649). CONCLUSION: As thyroid cancer incidence continues to increase, this study's finding that obesity was significantly associated with larger tumor size and marginally significantly associated with advanced tumor stage can help establish new preventative actions and identify new target populations for interventions.

Cancer of unknown primary: time trends in incidence, United States.

PURPOSE: To describe the epidemiological features and trends of cancer of unknown primary (CUP) in a large and diverse US population. METHODS: The Surveillance Epidemiology and End Results registry was used to examine incidence rates, adjusted to the World Segi 1960 population, by demographic and tumor characteristics among patients diagnosed with CUP between 1973 and 2010. Annual percent changes in incidence rates were estimated using Joinpoint regression. RESULTS: The incidence rate of pathologically investigated CUP was 4.1 per 100,000 and is consistent with reports from other countries. In the USA, CUP incidence rates have been decreasing since the early 1980s, 3.6 % per year in the last two decades. The USA experienced decreases earlier than other countries. US males and African Americans had the highest rates of CUP. The rates of non-microscopically confirmed CUP have dropped 2.6 % per year since 1973, but 24 % of CUP patients do not receive microscopic confirmation and 21 % of those with microscopically investigated cancer receive a vague histology (i.e., epithelial) diagnosis. Twenty percent of patients with pathological investigation receive radiation. Patients were twice as likely to be diagnosed with a non-pathologically investigated CUP if they were living in areas with the lowest income quartile relative to areas with the highest income quartile. CONCLUSION: Although the incidence of CUP is decreasing, we document CUP that may be due to insufficient diagnostic inquiry. Questions raised by the findings in this data provide hypotheses for further epidemiological and biological studies in the elucidation of CUP incidence and treatment.

Multiple primary tumors following stage II and III rectal cancer in patients receiving radiotherapy, 1998-2010.

OBJECTIVE: This report investigated the impact of radiation therapy among stage II/III rectal cancer patients who were resected for cure and then developed second primary cancer. METHODS: The analysis included patients diagnosed with rectal cancer from 1992 to 2010 and who were registered in the National Cancer Institute's Surveillance, Epidemiology and End Results database. Standardized incidence ratios assessed the location of second primary cancers by the receipt and sequence of radiation therapy. A Cox proportional hazards model examined the predictors for patients who developed second primary cancers. RESULTS: The hazard ratio for developing any type of second primary was 12 % higher in patients receiving preoperative radiotherapy, Hazard Ratio and 95 % confidence interval, HR 95 % CI 1.12 (1.0, 1.2), and 33 % lower for patients receiving postoperative radiotherapy, HR 95 % CI 0.75 (0.7, 0.8), relative to patients who did not receive radiation therapy. The location of the second cancer varied by both the receipt and sequence of radiation therapy. Secondary rectal cancers were reduced 170 % after postoperative radiation and 103 % after preoperative radiation, compared to the non-receipt of radiation therapy. The impact of radiation therapy on secondary colon cancers was not as marked. Rectal cancer patients undergoing radiation therapy are at a higher risk of thyroid cancers and leukemia, but males have a lower risk of prostate cancer. CONCLUSIONS: While preoperative radiation therapy is advantageous for reducing rectal cancer recurrence, this study identifies advantages of postoperative radiation for reducing second primary cancers. This research will help improve recommendations for postdiagnosis surveillance in patients with rectal cancer.