A Population-Based Study of Morbidity After Pancreatic Cancer Diagnosis.

BACKGROUND: Pancreatic cancer is an aggressive disease characterized by early and relentless tumor spread, thus leading healthcare providers to consider it a "distant disease." However, local pancreatic tumor progression can lead to substantial morbidity. This study defines the long-term morbidity from local and nonlocal disease progression in a large population-based cohort. METHODS: A total of 21,500 Medicare beneficiaries diagnosed with pancreatic cancer in 2000 through 2011 were identified. Hospitalizations were attributed to complications of either local disease (eg, biliary disorder, upper gastrointestinal ulcer/bleed, pain, pancreas-related, radiation toxicity) or nonlocal/distant disease (eg, thromboembolic events, cytopenia, dehydration, nausea/vomiting/motility problem, malnutrition and cachexia, ascites, pathologic fracture, and chemotherapy-related toxicity). Competing risk analyses were used to identify predictors of hospitalization. RESULTS: Of the total cohort, 9,347 patients (43.5%) were hospitalized for a local complication and 13,101 patients (60.9%) for a nonlocal complication. After adjusting for the competing risk of death, the 12-month cumulative incidence of hospitalization from local complications was highest in patients with unresectable disease (53.1%), followed by resectable (39.5%) and metastatic disease (33.7%) at diagnosis. For nonlocal complications, the 12-month cumulative incidence was highest in patients with metastatic disease (57.0%), followed by unresectable (56.8%) and resectable disease (42.8%) at diagnosis. Multivariable analysis demonstrated several predictors of hospitalization for local and nonlocal complications, including age, race/ethnicity, location of residence, disease stage, tumor size, and diagnosis year. Radiation and chemotherapy had minimal impact on the risk of hospitalization. CONCLUSIONS: Despite the widely known predilection of nonlocal/distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and frequent hospitalization.

Unplanned 30-day hospital readmission as a quality measure in gynecologic oncology.

OBJECTIVES: Thirty-day readmission is used as a quality measure for patient care and Medicare-based hospital reimbursement. The primary study objective was to describe the 30-day readmission rate to an academic gynecologic oncology service. Secondary objectives were to identify risk factors and costs related to readmission. METHODS: This was a retrospective, concurrent cohort study of all surgical admissions to an academic, high volume gynecologic oncology service during a two-year period (2013-2014). Data were collected on patient demographics, medical comorbidities, psychosocial risk factors, and results from a hospital discharge screening survey. Mixed logistic regression was used to identify factors associated with 30-day readmission and costs of readmission were assessed. RESULTS: During the two-year study period, 1605 women underwent an index surgical admission. Among this population, a total of 177 readmissions (11.0%) in 135 unique patients occurred. In a surgical subpopulation with >1 night stay, a readmission rate of 20.9% was observed. The mean interval to readmission was 11.8days (SD 10.7) and mean length of readmission stay was 5.1days (SD 5.0). Factors associated with readmission included radical surgery for ovarian cancer (OR 2.87) or cervical cancer (OR 4.33), creation of an ostomy (OR 11.44), a Charlson score of ≥5 (OR 2.15), a language barrier (OR 3.36), a median household income in the lowest quartile (OR 6.49), and a positive discharge screen (OR 2.85). The mean cost per readmission was $25,416 (SD $26,736), with the highest costs associated with gastrointestinal complications at $32,432 (SD $32,148). The total readmission-related costs during the study period were $4,523,959. CONCLUSIONS: Readmissions to a high volume gynecologic oncology service were costly and related to radical surgery for ovarian and cervical cancer as well as to medical, socioeconomic and psychosocial patient variables. These data may inform interventional studies aimed at decreasing unplanned readmissions in gynecologic oncology surgical populations.

Patterns of Palliative Care Consultation Among Elderly Patients With Cancer.

BACKGROUND: The role of palliative care has expanded over the past several decades, although the oncology-specific regional evolution of this specialty has not been characterized at the population-based level. METHODS: This study defined the patterns of palliative care delivery using a retrospective cohort of patients with advanced cancer within the SEER-Medicare linked database. We identified 83,022 patients with metastatic breast, prostate, lung, and colorectal cancers. We studied trends between 2000 through 2009, and determined patient-level and regional-level predictors of palliative care delivery. RESULTS: Palliative care consultation rates increased from 3.0% in 2000 to 12.9% in 2009, with most consultations occurring in the last 4 weeks of life (77%) in the inpatient hospital setting. The rates of palliative care delivery were highest in the West (7.6%) and lowest in the South (3.2%). The likelihood of palliative care consultation increased with decreasing numbers of regional acute care hospital beds per capita. The use of palliative care consultation increased with increasing numbers of regional physicians. The use of palliative care decreased with increasing regional Medicare expenditure with a $1,387 difference per beneficiary between the first and fourth quartiles of palliative care use. CONCLUSIONS: Geographic location influences a patient's options for palliative care in the United States. Although the overall rates of palliative care are increasing, future effort should focus on improving palliative care services in regions with the least access.

Dietary isoflavone intake is not statistically significantly associated with breast cancer risk in the Multiethnic Cohort.

Given the high intake levels of soya and low incidence rates of breast cancer in Asian countries, isoflavones, substances with an oestrogen-like structure occurring principally in soyabeans, are postulated to be cancer protective. In the present study, we examined the association of dietary isoflavone intake with breast cancer risk in 84,450 women (896 in situ and 3873 invasive cases) who were part of the Multiethnic Cohort (Japanese Americans, whites, Latinos, African Americans and Native Hawaiians) with a wide range of soya intake levels. The absolute levels of dietary isoflavone intake estimated from a baseline FFQ were categorised into quartiles, with the highest quartile being further subdivided to assess high dietary intake. The respective intake values for the quartiles (Q1, Q2, Q3, and lower and upper Q4) were 0-< 3·2, 3·2-< 6·7, 6·7-< 12·9, 12·9-< 20·3, and 20·3-178·7 mg/d. After a mean follow-up period of 13 years, hazard ratios (HR) and 95% CI were calculated using Cox regression models stratified by age and adjusted for known confounders. Linear trends were tested by modelling continuous variables of interest assigned the median value within the corresponding quartile. No statistically significant association was observed between dietary isoflavone intake and overall breast cancer risk (HR for upper Q4 v. Q1: 0·96 (95% CI 0·85, 1·08); P trend = 0·40). While the test for interaction was not significant (P=0·14), stratified analyses suggested possible ethnic/racial differences in risk estimates, indicating that higher isoflavone intakes may be protective in Latina, African American and Japanese American women. These results are in agreement with those of previous meta-analyses showing no protection of isoflavones at low intake levels, but suggesting inverse associations in populations consuming high amounts of soya.

Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. METHODS: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. FINDINGS: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). INTERPRETATION: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. FUNDING: Carraresi Foundation and others.

Clinical Outcomes and Healthcare Resource Utilization for Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents.

INTRODUCTION: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States. PATIENTS AND METHODS: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary ESA failure by SF3B1 mutational status, per recently updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines©). RESULTS: A total of 142 patients were included with a median follow-up time of 17 months (interquartile range [IQR], 7-33). Median age at ESA initiation was 79 years (IQR, 73-85). Patients were predominantly male (54%), overweight or obese (32% and 23%, respectively), of White race (96%) and non-Hispanic ethnicity (89%). Overall, 57% patients were initially treated with darbepoetin alfa and 43% with epoetin alfa. Clinical outcomes were poor, and there was a significant burden on both the health system and individual patients treated with ESA therapies. Hematologic improvement- erythroid was only seen in 26% of 142 patients treated with ESAs, and 65% of 82 retreated patients experienced primary ESA failure. CONCLUSION: Our results indicate that primary ESA failure is largely unrecognized and that many patients should be considered for alternative treatments.

Agreement for tumor grade of ovarian carcinoma: analysis of archival tissues from the surveillance, epidemiology, and end results residual tissue repository.

BACKGROUND: Emerging data suggest that ovarian cancers differ by tumor grade. However, the reliability of microscopic grade from paraffin tissue in the general medical community and as reflected in population-based cancer registries is unknown. METHODS: We examined grade agreement between two gynecologic pathologists and the Surveillance Epidemiology and End Results Residual Tissue Repository (SEER). Grade agreement was assessed with percent observer agreement and kappa coefficients for 664 invasive ovarian carcinomas, using previously defined three-tier and two-tier grading systems. A random subset of ovarian carcinomas was selected to compare intra- and inter-pathologist agreement. RESULTS: Five hundred and eighty-six of SEER's 664 tumors were confirmed invasive. Percent agreement was 49 % with fair kappa coefficient = 0.25 (95 % CI: 0.20-0.30) for the 664 tumors. Agreement improved slightly when restricted to the 586 confirmed invasive cancers; it was better for high grade than low grade tumors, for two-tier than three-tier grading systems, and within (66 %) than between study pathologists (43 %). Grade was not a robust independent predictor of ovarian cancer-specific survival. CONCLUSIONS: Grade agreement was fair between SEER and study pathologists irrespective of grading system. Recorded grade in SEER should be used with caution and is probably not a reliable metric for ovarian cancer epidemiology.

Racial and ethnic variation in the incidence of small-bowel cancer subtypes in the United States, 1995-2008.

BACKGROUND: Small-bowel cancer is uncommon and, accordingly, little is known about the epidemiology of this malignancy, especially by race and subtype. OBJECTIVE: The objective of this analysis was to describe the distribution of small-bowel cancer in the United States by demographic, pathological, and clinical features. DESIGN: This study was retrospective in design. SETTING: Data from 26 population-based cancer registries in the United States from 1995 to 2008 were used. PATIENTS: Patients diagnosed with small-bowel cancer (topography codes C17.0-17.3 and C17.8-17.9) were included. MAIN OUTCOME MEASURES: The primary outcomes measured were race- and histology-specific incidence (age-adjusted rate trends and age-specific rates) of small-bowel cancer. RESULTS: A total of 56,223 men and women diagnosed with small-bowel cancer were identified. The overall age-adjusted incidence rates for small-bowel cancer were 26.1 in men and 17.7 in women. Neuroendocrine tumors were the most common histological types of small-bowel cancer in men and women, followed by carcinoma, lymphoma, and sarcoma. In comparison with whites, the rate of small-bowel cancer was 42% greater in black men, 46% greater in black women, 34% lower in Asian-Pacific Islander men, and 37% lower in Asian-Pacific Islander women. Rates of small-bowel cancer were 24% lower in Hispanic men and 15% lower in Hispanic women than rates in non-Hispanics. The excess of small-bowel cancer in blacks and the deficit in Asian-Pacific Islanders were attributable mainly to the incidence of adenocarcinoma and carcinoid tumors. The incidence of GI stromal tumor was significantly higher among Asian-Pacific Islanders. CONCLUSIONS: This is one of the largest studies of small-bowel cancer to date. These cancer registry data showed substantial racial and ethnic variation in the incidence of histological subtypes of small-bowel malignancy that suggest possible etiologic diversity and/or disparities in detection.

Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium.

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P(trend) < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years.

Cervical cancer screening compliance among active duty service members in the US military.

Previous research suggests active duty service members (ADSM) experience higher rates of human papilloma virus infection and cervical dysplasia, which puts them at greater risk for cervical cancer. The current study examined crude rates and correlates of cervical cancer screening compliance in 2003-2015 among screening-eligible ADSM in the Millennium Cohort Study (MCS). Data were drawn from the MCS, Defense Manpower Data Center, and Military Health System Data Repository. Screening eligibility and compliance were calculated each year and initial analyses examined crude rates of compliance. Generalized estimating equations were calculated to determine whether sociodemographic, military, and mental/behavioral health covariates were associated with cervical cancer screening compliance. A majority of participants were 21-29 years old (79.4%), non-Hispanic White (60.6%), and enlisted (82.2%). Crude rates of cervical cancer screening compliance increased from 2003 (61.2%) to 2010 (83.1%), and then declined from 2010 to 2015 (59.8%). Older ADSM and those who had a history of deployment had lower odds of screening compliance. ADSM in the Air Force and those in healthcare occupations had higher odds of screening compliance. Study findings suggest that cervical cancer screening compliance is declining among ADSM. Interventions to improve screening should target groups with lower screening compliance.

Factors Associated with Human Papillomavirus Vaccine Initiation and Compliance Among U.S. Military Service Members.

INTRODUCTION: The primary objective of the current study was to assess factors associated with Human Papillomavirus (HPV) vaccine initiation and compliance in a cohort of active duty US military service members (SM). MATERIALS AND METHODS: We included active-duty participants aged 18-26 years from the Millennium Cohort Study, a longitudinal cohort study of over 200,000 military SMs. The eligible study population included 22,387 female SMs and 31,705 male SMs. Vaccination was assessed over the period 2006-2017. Logistic regression was used to estimate the odds of vaccine initiation and compliance (3 doses within a 1-year period) in relation to demographic, military, health, and behavioral characteristics. RESULTS: Among female SMs, 37.8% initiated the vaccine and 40.2% of initiators completed the series within a year. Among male SMs, 3.9% initiated the vaccine and 22.1% of initiators completed the series within a year. Differences by sociodemographic factors, deployment status, branch of service, occupation, and smoking status-but not by selected mental health conditions-were observed. CONCLUSION: HPV vaccination uptake is subpar across all military service branches. Certain subgroups of SMs could be targeted to increase overall HPV vaccine coverage in the US military population.

The Millennium Cohort Study: The first 20 years of research dedicated to understanding the long-term health of US Service Members and Veterans.

PURPOSE: The Millennium Cohort Study, the US Department of Defense's largest and longest running study, was conceived in 1999 to investigate the effects of military service on service member health and well-being by prospectively following active duty, Reserve, and National Guard personnel from all branches during and following military service. In commemoration of the Study's 20th anniversary, this paper provides a summary of its methods, key findings, and future directions. METHODS: Recruitment and enrollment of the first 5 panels occurred between 2001 and 2021. After completing a baseline survey, participants are requested to complete follow-up surveys every 3-5 years. RESULTS: Study research projects are categorized into 3 core portfolio areas (psychological health, physical health, and health-related behaviors) and several cross-cutting areas and have culminated in more than 120 publications to date. For example, some key Study findings include that specific military service-related factors (e.g., experiencing combat, serving in certain occupational subgroups) were associated with adverse health-related outcomes and that unhealthy behaviors and mental health issues may increase following the transition from military service to veteran status. CONCLUSIONS: The Study will continue to foster stakeholder relationships such that research findings inform and guide policy initiatives and health promotion efforts.

Association of Combat Experiences With Suicide Attempts Among Active-Duty US Service Members.

Importance: There is uncertainty about the role that military deployment experiences play in suicide-related outcomes. Most previous research has defined combat experiences broadly, and a limited number of cross-sectional studies have examined the association between specific combat exposure (eg, killing) and suicide-related outcomes. Objective: To prospectively examine combat exposures associated with suicide attempts among active-duty US service members while accounting for demographic, military-specific, and mental health factors. Design, Setting, and Participants: This cohort study analyzed data from the Millennium Cohort Study, an ongoing prospective longitudinal study of US service members from all military branches. Participants were enrolled in 4 phases from July 1, 2001, to April 4, 2013, and completed a self-administered survey at enrollment and every 3 to 5 years thereafter. The population for the present study was restricted to active-duty service members from the first 4 enrollment phases who deployed in support of the wars in Iraq and Afghanistan. Questionnaire data were linked with medical encounter data through September 30, 2015. Data analyses were conducted from January 10, 2017, to December 14, 2020. Exposures: Combat exposure was examined in 3 ways (any combat experience, overall combat severity, and 13 individual combat experiences) using a 13-item self-reported combat measure. Main Outcomes and Measures: Suicide attempts were identified from military electronic hospitalization and ambulatory medical encounter data using the International Classification of Diseases, Ninth Revision codes. Results: Among 57 841 participants, 44 062 were men (76.2%) and 42 095 were non-Hispanic White individuals (72.8%), and the mean (SD) age was 26.9 (5.3) years. During a mean (SD) follow-up period of 5.6 (4.0) years, 235 participants had a suicide attempt (0.4%). Combat exposure, defined broadly, was not associated with suicide attempts in Cox proportional hazards time-to-event regression models after adjustments for demographic and military-specific factors; high combat severity and certain individual combat experiences were associated with an increased risk for suicide attempts. However, these associations were mostly accounted for by mental disorders, especially posttraumatic stress disorder. After adjustment for mental disorders, combat experiences with significant association with suicide attempts included being attacked or ambushed (hazard ratio [HR], 1.55; 95% CI, 1.16-2.06), seeing dead bodies or human remains (HR, 1.34; 95% CI, 1.01-1.78), and being directly responsible for the death of a noncombatant (HR, 1.81; 95% CI, 1.04-3.16). Conclusions and Relevance: This study suggests that deployed service members who experience high levels of combat or are exposed to certain types of combat experiences (involving unexpected events or those that challenge moral or ethical norms) may be at an increased risk of a suicide attempt, either directly or mediated through a mental disorder.

Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics.

The transforming growth factor beta (TGF-beta) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-beta signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case-control study conducted in Poland from 2000 to 2003. TGF-beta signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-beta1 (78%), TGF-beta2 (91%), TGF-beta3 (93%), TGF-betaR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-beta1 was expressed in 32% of tumors. Expression of TGF-beta ligands (beta1, beta2, and beta3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-betaR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-beta. In addition, expression of extracellular-TGF-beta1 (P = 0.005), TGF-betaR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment.

Symptom presentation in invasive ovarian carcinoma by tumor histological type and grade in a multiethnic population: a case analysis.

OBJECTIVE: Although the majority of women with ovarian carcinoma report symptoms prior to diagnosis, little is known about comparative symptom presentation by histological type, stage, grade, or ethnicity. METHODS: We conducted a population-based study including 622 women with invasive ovarian carcinoma diagnosed from 1993 to 2008. Epidemiological and symptom data were collected using an interviewer-administered questionnaire. Symptoms established as significant predictors of ovarian carcinoma were examined in relation to patient and tumor characteristics, using unconditional multivariate logistic regression and general linear models. RESULTS: Symptom presentation and duration differed significantly among women with ovarian carcinoma by stage, tumor histology, and grade, but not ethnicity. Significant differences were observed by histology in reporting a distended abdomen, abnormal vaginal bleeding, and bowel symptoms. Compared to women diagnosed with serous carcinoma, women with mucinous tumors were 2.6 times more likely to report a distended abdomen; women with endometrioid carcinoma were three times more likely to report abnormal bleeding. Women with serous tumors were significantly more likely to report bowel symptoms than were women diagnosed with other histological types. The majority of women with serous tumors were diagnosed with advanced cancer and had shorter duration of symptoms than women with early stage disease. In contrast, women with mucinous tumors were generally diagnosed at an early stage and had longer duration of symptoms (p=0.009) if diagnosed at an advanced stage. CONCLUSION: The study provides evidence that the early diagnosis of ovarian cancer is largely determined by tumor histological type.

Hairy cell leukaemia: a heterogeneous disease?

The US National Cancer Institute's Surveillance, Epidemiology and End Results program was used to develop aetiological clues for hairy cell leukaemia (HCL). Descriptive techniques (age-adjusted incidence trends, age-specific incidence rates (IR), and age distributions-at-diagnosis) were supplemented with mathematical models (two-component mixture, generalized linear regression, and age-period-cohort). There were 2856 cases of HCL diagnosed during 1978-2004 (IR 0.32/100,000 person-years). IRs were nearly 4-fold greater among men than women and more than 3-fold higher for Whites than Blacks. Temporal trends were stable over time. Age-specific IRs increased rapidly until approximately 40 years then rose at a slower pace. The age-specific IR curves reflected bimodal early- and late-onset age distributions-at-diagnosis (or density plots), with some variation by gender. Among both men and women, a two-component mixture model fitted the data better than a single density or cancer population. Age-period-cohort models confirmed statistically significant age-related effects after full adjustment for temporal trends (calendar-period and birth-cohort effects). In summary, age incidence patterns (rates and bimodal densities) suggested that HCL is a heterogeneous disease, consisting of at least two underlying subgroups and/or cancer populations by age-at-onset. Distinct early- and late-onset HCL populations may reflect different age-related causal pathways, risk factor profiles, and/or stem cells of origin.

Early- and late-onset breast cancer types among women in the United States and Japan.

BACKGROUND: Although differences in breast cancer incidence among Occidental and Asian populations are often attributed to variations in environmental exposures and/or lifestyle, fewer studies have systematically examined the effect of age-related variations. METHODS: To further explore age-related geographic breast cancer variations, we compared age-specific incidence patterns among cases of female invasive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) program and the Osaka Cancer Registry (1978-1997). RESULTS: In SEER, there were 236,130 Whites, 21,137 Blacks, and 3,304 Japanese-Americans in Hawaii with invasive breast cancer. In Osaka, there were 25,350 cases. Incidence rates per 100,000 woman-years ranged from 87.6 among Whites to 21.8 in Osaka. Age-specific incidence rates increased rapidly until age 50 years for all race/ethnicity groups, and then continued to increase more slowly for Whites, Blacks, and Japanese-Americans in Hawaii but plateaud for Osaka. Age-specific incidence rates in SEER reflected bimodal (early-onset and late-onset) breast cancer populations, whereas Osaka had only an early-onset age distribution. These age-specific differences in incidence among SEER and Osaka persisted after adjustment for calendar-period and birth-cohort effects using age-period-cohort models. CONCLUSIONS: Results confirm striking age-specific differences among Occidental and native Japanese breast cancer populations, probably due to complex age-related biological and/or environmental variations among Occidental and Asian breast cancer populations.

Effect of Palliative Care on Aggressiveness of End-of-Life Care Among Patients With Advanced Cancer.

PURPOSE: Palliative care's role in oncology has expanded, but its effect on aggressiveness of care at the end of life has not been characterized at the population level. METHODS: This matched retrospective cohort study examined the effect of an encounter with palliative care on health-care use at the end of life among 6,580 Medicare beneficiaries with advanced prostate, breast, lung, or colorectal cancer. We compared health-care use before and after palliative care consultation to a matched nonpalliative care cohort. RESULTS: The palliative care cohort had higher rates of health-care use in the 30 days before palliative care consultation compared with the nonpalliative cohort, with higher rates of hospitalization (risk ratio [RR], 3.33; 95% CI, 2.87 to 3.85), invasive procedures (RR, 1.75; 95% CI, 1.62 to 1.88), and chemotherapy administration (RR, 1.61; 95% CI, 1.45 to 1.78). The opposite pattern emerged in the interval from palliative care consultation through death, where the palliative care cohort had lower rates of hospitalization (RR, 0.53; 95% CI, 0.44-0.65), invasive procedures (RR, 0.52; 95% CI, 0.45 to 0.59), and chemotherapy administration (RR, 0.46; 95% CI, 0.39 to 0.53). Patients with earlier palliative care consultation in their disease course had larger absolute reductions in health-care use compared with those with palliative care consultation closer to the end of life. CONCLUSION: This population-based study found that palliative care substantially decreased health-care use among Medicare beneficiaries with advanced cancer. Given the increasing number of elderly patients with advanced cancer, this study emphasizes the importance of early integration of palliative care alongside standard oncologic care.

Geographic Disparity in the Use of Hypofractionated Radiation Therapy Among Elderly Women Undergoing Breast Conservation for Invasive Breast Cancer.

PURPOSE: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States. METHODS AND MATERIALS: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT. RESULTS: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements. CONCLUSIONS: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery.