Neoadjuvant FOLFIRINOX for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer: Results of a Decision Analysis.

BACKGROUND: The effectiveness and cost-effectiveness of using neoadjuvant FOLFIRINOX (nFOLFIRINOX) for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC) are unknown. Our objective was to determine whether nFOLFIRINOX is more effective or cost-effective for patients with BR/LA PDAC compared with upfront resection surgery and adjuvant gemcitabine plus capecitabine (GEM/CAPE) or gemcitabine monotherapy (GEM). MATERIALS AND METHODS: We performed a decision-analysis to assess the value of nFOLFIRINOX versus GEM/CAPE or GEM using a mathematical simulation model. Model transition probabilities were estimated using published and institutional clinical data. Model outcomes included overall and disease-free survival, quality-adjusted life-years (QALYs), cost in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses explored the uncertainty of model assumptions. RESULTS: Model results found median overall survival (34.5/28.0/22.0 months) and disease-free survival (15.0/14.0/13.0 months) were better for nFOLFIRINOX compared with GEM/CAPE and GEM. nFOLFIRINOX was the optimal strategy on an efficiency frontier, resulting in an additional 0.35 life-years, or 0.30 QALYs, at a cost of $46,200/QALY gained compared with GEM/CAPE. Sensitivity analysis found that cancer recurrence and complete resection rates most affected model results, but were otherwise robust. Probabilistic sensitivity analyses found that nFOLFIRINOX was cost-effective 92.4% of the time at a willingness-to-pay threshold of $100,000/QALY. CONCLUSION: Our modeling analysis suggests that nFOLFIRINOX is preferable to upfront surgery for patients with BR/LA PDAC from both an effectiveness and cost-effectiveness standpoint. Additional clinical data that further define the long-term effectiveness of nFOLFIRINOX are needed to confirm our results. IMPLICATIONS FOR PRACTICE: Increasingly, neoadjuvant FOLFIRINOX has been used for borderline resectable and locally advanced pancreatic cancer with the goal of rendering them resectable and decreasing risk of recurrence. Despite many efforts to show the benefits of neoadjuvant over adjuvant therapies, clinical evidence to guide this decision is largely lacking. Decision-analytic modeling can provide a methodologic platform that integrates the best available data to quantitatively explore clinical decisions by simulating a hypothetical clinical trial. This modeling analysis suggests that neoadjuvant FOLFIRINOX is preferable to upfront surgery and adjuvant therapies by various outcome metrics including quality-adjusted life years, overall survival, and incremental cost-effectiveness ratio.

Impact of sociodemographic characteristics on underemployment in a longitudinal, nationally representative study of cancer survivors: Evidence for the importance of gender and marital status.

BACKGROUND: We examined the longitudinal association between sociodemographic factors and an expanded definition of underemployment among those with and without cancer history in the United States. METHODS: Medical Expenditure Panel Survey data (2007-2013) were used in multivariable regression analyses to compare employment status between baseline and two-year follow-up among adults aged 25-62 years at baseline (n = 1,614 with and n = 39,324 without cancer). Underemployment was defined as becoming/staying unemployed, changing from full to part-time, or reducing part-time work significantly. Interaction effects between cancer history/time since diagnosis and predictors known to be associated with employment patterns, including age, gender/marital status, education, and health insurance status at baseline were modeled. RESULTS: Approximately 25% of cancer survivors and 21% of individuals without cancer reported underemployment at follow-up (p = 0.002). Multivariable analyses indicated that those with a cancer history report underemployment more frequently (24.7%) than those without cancer (21.4%, p = 0.002) with underemployment rates increasing with time since cancer diagnosis. A significant interaction between gender/marital status and cancer history and underemployment was found (p = 0.0004). There were no other significant interactions. Married female survivors diagnosed >10 years ago reported underemployment most commonly (38.7%), and married men without cancer reported underemployment most infrequently (14.0%). A wider absolute difference in underemployment reports for married versus unmarried women as compared to married versus unmarried men was evident, with the widest difference apparent for unmarried versus married women diagnosed >10 years ago (18.1% vs. 38.7%). CONCLUSION: Cancer survivors are more likely to experience underemployment than those without cancer. Longer time since cancer diagnosis and gender/marital status are critical factors in predicting those at greatest risk of underemployment. The impact of cancer on work should be systematically studied across sociodemographic groups and recognized as a component of comprehensive survivorship care.

Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device.

BACKGROUND & AIMS: It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could be a cost-effective tool for screening individuals with gastroesophageal reflux disease (GERD) who are at increased risk for BE. We developed a model to analyze the cost effectiveness of using the Cytosponge in first-line screening of patients with GERD for BE with endoscopic confirmation, compared with endoscopy screening only. METHODS: We incorporated data from a large clinical trial of Cytosponge performance into 2 validated microsimulation models of EAC progression (the esophageal adenocarcinoma model from Massachusetts General Hospital and the microsimulation screening analysis model from Erasmus University Medical Center). The models were calibrated for US Surveillance, Epidemiology and End Results data on EAC incidence and mortality. In each model, we simulated the effect of a 1-time screen for BE in male patients with GERD, 60 years of age, using endoscopy alone or Cytosponge collection of tissue, and analysis for the level of trefoil factor 3 with endoscopic confirmation of positive results. For each strategy we recorded the number of cases of EAC that developed, the number of EAC cases detected with screening by Cytosponge only or by subsequent targeted surveillance, and the number of endoscopies needed. In addition, we recorded the cumulative costs (including indirect costs) incurred and quality-adjusted years of life lived within each strategy, discounted at a rate of 3% per year, and computed incremental cost-effectiveness ratios (ICERs) among the 3 strategies. RESULTS: According to the models, screening patients with GERD by Cytosponge with follow-up confirmation of positive results by endoscopy would reduce the cost of screening by 27% to 29% compared with screening by endoscopy, but led to 1.8 to 5.5 (per 1000 patients) fewer quality-adjusted life years. The ICERs for Cytosponge screening compared with no screening ranged from $26,358 to $33,307. For screening patients by endoscopy compared with Cytosponge the ICERs ranged from $107,583 to $330,361. These results were sensitive to Cytosponge cost within a plausible range of values. CONCLUSIONS: In a comparative modeling analysis of screening strategies for BE in patients with GERD, we found Cytosponge screening with endoscopic confirmation to be a cost-effective strategy. The greatest benefit was achieved by endoscopic screening, but with an unfavorable cost margin.

The Impact of a Prior Diagnosis of Barrett's Esophagus on Esophageal Adenocarcinoma Survival.

OBJECTIVES: Endoscopic surveillance of patients with Barrett's Esophagus (BE) is recommended to detect esophageal adenocarcinoma (EAC) and its dysplasia precursors, but survival benefits are unclear. Using Surveillance, Epidemiology, and End Results (SEER) and linked Medicare data, we sought to determine the impact of a prior BE diagnosis on survival in patients with EAC. METHODS: Our analysis focused on patients over age 65 with primary EAC diagnosed in a SEER region from 2000-2011 and enrolled in Medicare. We identified patients with preexisting BE prior to EAC diagnosis and compared this group to EAC patients without a prior BE diagnosis. A Cox Proportional Hazards model compared survival and included variables such as age, sex, cancer stage, treatment, and medical comorbidities. RESULTS: Among 4,978 SEER-Medicare patients identified with EAC, 577 (12%) had preexisting BE; 4,401 (88%) did not. BE patients had overall lower stage (28.5% stage I vs. 12.8% stage IV) than those without preexisting BE (16.4% stage I vs. 30.6% stage IV). Overall survival was better among patients in the BE group (hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.50-0.61); this benefit persisted in the adjusted model (HR, 0.72; 95%, 0.65-0.80). After adjusting for lead-time bias, the HRs attenuated to the null, with an unadjusted HR of 0.96 (95% CI: 0.86-1.05, P=0.39) and adjusted HR of 0.99 (CI: 0.89-1.10, P=0.92). CONCLUSIONS: Survival outcomes in patients with a BE diagnosis prior to EAC were statistically better in both the unadjusted and adjusted Cox proportional hazards model. However, this benefit appears to be predominantly lead-time and length-time bias.

Role of CT in the Diagnosis of Nonspecific Abdominal Pain: A Multicenter Analysis.

OBJECTIVE: The objective of our study was to determine whether specific patient and physician factors-known before CT-are associated with a diagnosis of nonspecific abdominal pain (NSAP) after CT in the emergency department (ED). MATERIALS AND METHODS: We analyzed data originally collected in a prospective multicenter study. In the parent study, we identified ED patients referred to CT for evaluation of abdominal pain. We surveyed their physicians before and after CT to identify changes in leading diagnoses, diagnostic confidence, and admission decisions. In the current study, we conducted a multiple regression analysis to identify whether the following were associated with a post-CT diagnosis of NSAP: patient age; patient sex; physicians' years of experience; physicians' pre-CT diagnostic confidence; and physicians' pre-CT admission decision if CT had not been available. We analyzed patients with and those without a pre-CT diagnosis of NSAP separately. For the sensitivity analysis, we excluded patients with different physicians before and after CT. RESULTS: In total, 544 patients were included: 10% (52/544) with a pre-CT diagnosis of NSAP and 90% (492/544) with a pre-CT diagnosis other than NSAP. The leading diagnoses changed after CT in a large proportion of patients with a pre-CT diagnosis of NSAP (38%, 20/52). In regression analysis, we found that physicians' pre-CT diagnostic confidence was inversely associated with a post-CT diagnosis of NSAP in patients with a pre-CT diagnosis other than NSAP (p = 0.0001). No other associations were significant in both primary and sensitivity analyses. CONCLUSION: With the exception of physicians' pre-CT diagnostic confidence, the factors evaluated were not associated with a post-CT diagnosis of NSAP.

Changes in Physician Decision Making after CT: A Prospective Multicenter Study in Primary Care Settings.

Purpose To determine the effect of computed tomography (CT) results on physician decision making in three common clinical scenarios in primary care. Materials and Methods This research was approved by the institutional review board (IRB) and was HIPAA compliant. All physicians consented to participate with an opt-in or opt-out mechanism; patient consent was waived with IRB approval. In this prospective multicenter observational study, outpatients referred by primary care providers (PCPs) for CT evaluation of abdominal pain, hematuria, or weight loss were identified. Prior to CT, PCPs were surveyed to elicit their leading diagnosis, confidence in that diagnosis (confidence range, 0%-100%), a rule-out diagnosis, and a management plan if CT were not available. Surveys were repeated after CT. Study measures were the proportion of patients in whom leading diagnoses and management changed (PCP management vs specialist referral vs emergency department transfer), median changes in diagnostic confidence, and the proportion of patients in whom CT addressed rule-out diagnoses. Regression analyses were used to identify associations between study measures and site and participant characteristics. Specifically, logistic regression analysis was used for binary study measures (change in leading diagnosis, change in management), and linear regression analysis was used for the continuous study measure (change in diagnostic confidence). Accrual began on September 5, 2012, and ended on June 28, 2014. Results In total, 91 PCPs completed pre- and post-CT surveys in 373 patients. In patients with abdominal pain, hematuria, or weight loss, leading diagnoses changed after CT in 53% (131 of 246), 49% (36 of 73), and 57% (27 of 47) of patients, respectively. Management changed in 35% (86 of 248), 27% (20 of 74), and 54% (26 of 48) of patients, respectively. Median absolute changes in diagnostic confidence were substantial and significant (+20%, +20%, and +19%, respectively; P ≤ .001 for all); median confidence after CT was high (90%, 88%, and 80%, respectively). PCPs reported CT was helpful in confirming or excluding rule-out diagnoses in 98% (184 of 187), 97% (59 of 61), and 97% (33 of 34) of patients, respectively. Significant associations between primary measures and site and participant characteristics were not identified. Conclusion Changes in PCP leading diagnoses and management after CT were common, and diagnostic confidence increased substantially. © RSNA, 2016 Online supplemental material is available for this article.

CT in the Emergency Department: A Real-Time Study of Changes in Physician Decision Making.

PURPOSE: To determine how physicians' diagnoses, diagnostic uncertainty, and management decisions are affected by the results of computed tomography (CT) in emergency department settings. MATERIALS AND METHODS: This study was approved by the institutional review board and compliant with HIPAA. Data were collected between July 12, 2012, and January 13, 2014. The requirement to obtain patient consent was waived. In this prospective, four-center study, patients presenting to the emergency department who were referred for CT with abdominal pain, chest pain and/or dyspnea, or headache were identified. Physicians were surveyed before and after CT to determine the leading diagnosis, diagnostic confidence (on a scale of 0% to 100%), alternative "rule out" diagnosis, and management decisions. Primary measures were the proportion of patients for whom the leading diagnosis or admission decision changed and median changes in diagnostic confidence. Secondary measures addressed alternative diagnoses and return-to-care visits (eg, to emergency department) at 1-month follow-up. Regression analysis was used to identify associations between primary measures and site and participant characteristics. RESULTS: Both surveys were completed for 1280 patients by 245 physicians. The leading diagnosis changed in 235 of 460 patients with abdominal pain (51%), 163 of 387 with chest pain and/or dyspnea (42%), and 103 of 433 with headache (24%). Pre-CT diagnostic confidence was inversely associated with the likelihood of a diagnostic change (P < .0001). Median changes in confidence were substantial (increases of 25%, 20%, and 13%, respectively, for patients with abdominal pain, chest pain and/or dyspnea, and headache; P < .0001); median post-CT confidence was high (95% for all three groups). CT helped confirm or exclude at least 95% of alternative diagnoses. Admission decisions changed in 116 of 457 patients with abdominal pain (25%), 72 of 387 with chest pain and/or dyspnea (19%), and 81 of 426 with headache (19%). During follow-up, 70 of 450 patients with abdominal pain (15%), 53 of 387 with chest pain and/or dyspnea (14%), and 49 of 433 with headache (11%) returned for the same indication. In general, changes in leading diagnosis, diagnostic confidence, and admission decisions were not well explained with site or participant characteristics. CONCLUSION: Physicians' diagnoses and admission decisions changed frequently after CT, and diagnostic uncertainty was alleviated.

Targeted screening of individuals at high risk for pancreatic cancer: results of a simulation model.

PURPOSE: To identify when, from the standpoint of relative risk, magnetic resonance (MR) imaging-based screening may be effective in patients with a known or suspected genetic predisposition to pancreatic cancer. MATERIALS AND METHODS: The authors developed a Markov model of pancreatic ductal adenocarcinoma (PDAC). The model was calibrated to National Cancer Institute Surveillance, Epidemiology, and End Results registry data and informed by the literature. A hypothetical screening strategy was evaluated in which all population individuals underwent one-time MR imaging screening at age 50 years. Screening outcomes for individuals with an average risk for PDAC ("base case") were compared with those for individuals at an increased risk to assess for differential benefits in populations with a known or suspected genetic predisposition. Effects of varying key inputs, including MR imaging performance, surgical mortality, and screening age, were evaluated with a sensitivity analysis. RESULTS In the base case, screening resulted in a small number of cancer deaths averted (39 of 100 000 men, 38 of 100 000 women) and a net decrease in life expectancy (-3 days for men, -4 days for women), which was driven by unnecessary pancreatic surgeries associated with false-positive results. Life expectancy gains were achieved if an individual's risk for PDAC exceeded 2.4 (men) or 2.7 (women) times that of the general population. When relative risk increased further, for example to 30 times that of the general population, averted cancer deaths and life expectancy gains increased substantially (1219 of 100 000 men, life expectancy gain: 65 days; 1204 of 100 000 women, life expectancy gain: 71 days). In addition, results were sensitive to MR imaging specificity and the surgical mortality rate. CONCLUSION: Although PDAC screening with MR imaging for the entire population is not effective, individuals with even modestly increased risk may benefit.

Trends in esophageal adenocarcinoma incidence and mortality.

BACKGROUND: Over the past several decades, the incidence of esophageal adenocarcinoma (EAC) has rapidly increased. The purpose of this analysis was to examine temporal trends in EAC incidence and mortality within the US population and, in addition, to explore these trends within subgroups of the population. METHODS: The National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER 9) data were used to examine incidence and incidence-based (IB) mortality in EAC from 1975 to 2009. Secular trends in incidence and IB mortality by cancer stage, sex, and race were further characterized using the NCI's Joinpoint Regression program. RESULTS: Based on SEER 9 data, EAC incidence and IB mortality continues to increase in the United States. However, since the mid-1990s, the overall rate of increase in both EAC incidence and IB mortality appears to be slowing. In addition, in early-stage cancers, there is a noticeable leveling off of IB mortality rates and divergence from incidence starting in the late 1990s. Over the study period, the average annual percentage increase in incidence was 6.1% in men and 5.9% in women. CONCLUSIONS: EAC incidence and IB mortality rates continue to rise in the United States, although at a slower rate in more recent years. In early-stage cancers, IB mortality and incidence rates have diverged primarily because IB mortality rates have plateaued beginning in the late 1990s. Although EAC continues to be less common in women, the rate of increase in EAC incidence is similar in both sexes.

Lost productivity and burden of illness in cancer survivors with and without other chronic conditions.

BACKGROUND: Cancer survivors may experience long-term and late effects from treatment that adversely affect health and limit functioning. Few studies examine lost productivity and disease burden in cancer survivors compared with individuals who have other chronic conditions or by cancer type. METHODS: We identified 4960 cancer survivors and 64,431 other individuals from the 2008-2010 Medical Expenditure Panel Survey and compared multiple measures of disease burden, including health status and lost productivity, between conditions and by cancer site for cancer survivors. All analyses controlled for the effects of age, sex, race/ethnicity, and number of comorbid conditions. RESULTS: Overall, in adjusted analyses in multiple models, cancer survivors with another chronic disease (heart disease or diabetes) experienced higher levels of burden compared with individuals with a history of cancer only, chronic disease only, and neither cancer, heart disease, nor diabetes across multiple measures (P < .05). Among cancer survivors, individuals with short survival cancers and multiple cancers consistently had the highest levels of burden across multiple measures (P < .0001). CONCLUSIONS: Cancer survivors who have another chronic disease experience more limitations and higher levels of burden across multiple measures. Limitations are particularly severe in cancer survivors with short survival cancer and multiple cancers.

Journal club: How radiation exposure histories influence physician imaging decisions: a multicenter radiologist survey study.

OBJECTIVE: The purpose of this article is to evaluate the influence of patient radiation exposure histories on radiologists' imaging decisions. MATERIALS AND METHODS: We conducted a physician survey study in three academic medical centers. Radiologists were asked to make an imaging recommendation for a hypothetical patient with a history of multiple CT scans. We queried radiologists' decision making, evaluating whether they incorporated cancer risks from previous imaging, reported acceptance (or rejection) of the linear no-threshold model, and understood linear no-threshold model implications in this setting. Consistency between radiologists' decisions and their linear no-threshold model beliefs was evaluated; those acting in accordance with the linear no-threshold model were expected to disregard previously incurred cancer risks. A Fisher exact test was used to verify the generalizability of results across institutions and training levels (residents, fellows, and attending physicians). RESULTS: Fifty-six percent (322/578) of radiologists completed the survey. Most (92% [295/322]) incorporated risks from the patient's exposure history during decision making. Most (61% [196/322]) also reported acceptance of the linear no-threshold model. Fewer (25% [79/322]) rejected the linear no-threshold model; 15% (47/322) could not judge. Among radiologists reporting linear no-threshold model acceptance or rejection, the minority (36% [98/275]) made decisions that were consistent with their linear no-threshold model beliefs. This finding was not statistically different across institutions (p = 0.070) or training levels (p = 0.183). Few radiologists (4% [13/322]) had an accurate understanding of linear no-threshold model implications. CONCLUSION: Most radiologists, when faced with patient exposure histories, make decisions that contradict their self-reported acceptance of the linear no-threshold model and the linear no-threshold model itself. These findings underscore a need for educational initiatives.

Disparities in cancer outcomes across age, sex, and race/ethnicity among patients with pancreatic cancer.

Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine whether survival and treatment disparities persist after adjusting for demographic and clinical characteristics. Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox regression to compare survival across age, sex, and race/ethnicity within early-stage and late-stage cancer subgroups, adjusting for marital status, urban location, socioeconomics, SEER region, comorbidities, stage, lymph node status, tumor location, tumor grade, diagnosis year, and treatment received. We used logistic regression to compare differences in treatment received across age, sex, and race/ethnicity. Among 20,896 patients, 84% were White, 9% Black, 5% Asian, and 2% Hispanic. Median age was 75; 56% were female and 53% had late-stage cancer. Among early-stage patients in the adjusted Cox model, older patient subgroups had worse survival compared with ages 66-69 (HR > 1.1, P < 0.01 for groups >69); no survival differences existed between sexes. Black (HR = 1.1, P = 0.01) and Hispanic (HR = 1.2, P < 0.01) patients had worse survival compared with White. Among late-stage cancer patients, patients over age 84 had worse survival than those aged 66-69 (HR = 1.1, P < 0.01), and males (HR = 1.08, P < 0.01) had worse survival than females; there were no racial/ethnic differences. Older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Age and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC patients; these disparities persist after adjusting for differences in demographic and clinical characteristics.

Employment implications of informal cancer caregiving.

PURPOSE: Previous research describing how informal cancer caregiving impacts employment has been conducted in small samples or a single disease site. This paper provides population-based estimates of the effect of informal cancer caregiving on employment and characterizes employment changes made by caregivers. METHODS: The samples included cancer survivors with a friend or family caregiver, participating in either the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Survey (ECSS) (n = 458) or the LIVESTRONG 2012 Survey for People Affected by Cancer (SPAC) (n = 4706). Descriptive statistics characterized the sample of survivors and their caregivers' employment changes. Multivariable logistic regression identified predictors of caregivers' extended employment changes, comprising time off and changes to hours, duties, or employment status. RESULTS: Among survivors with an informal caregiver, 25 % from the ECSS and 29 % from the SPAC reported that their caregivers made extended employment changes. Approximately 8 % of survivors had caregivers who took time off from work lasting ≥2 months. Caregivers who made extended employment changes were more likely to care for survivors: treated with chemotherapy or transplant; closer to diagnosis or end of treatment; who experienced functional limitations; and made work changes due to cancer themselves compared to caregivers who did not make extended employment changes. CONCLUSIONS: Many informal cancer caregivers make employment changes to provide care during survivors' treatment and recovery. IMPLICATIONS FOR CANCER SURVIVORS: This study describes cancer caregiving in a prevalent sample of cancer survivors, thereby reflecting the experiences of individuals with many different cancer types and places in the cancer treatment trajectory.

Evaluating the impacts of screening and smoking cessation programmes on lung cancer in a high-burden region of the USA: a simulation modelling study.

OBJECTIVE: While the US Preventive Services Task Force has issued recommendations for lung cancer screening, its effectiveness at reducing lung cancer burden may vary at local levels due to regional variations in smoking behaviour. Our objective was to use an existing model to determine the impacts of lung cancer screening alone or in addition to increased smoking cessation in a US region with a relatively high smoking prevalence and lung cancer incidence. SETTING: Computer-based simulation model. PARTICIPANTS: Simulated population of individuals 55 and older based on smoking prevalence and census data from Northeast Pennsylvania. INTERVENTIONS: Hypothetical lung cancer control from 2014 to 2050 through (1) screening with CT, (2) intensified smoking cessation or (3) a combination strategy. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were lung cancer mortality rates. Secondary outcomes included number of people eligible for screening and number of radiation-induced lung cancers. RESULTS: Combining lung cancer screening with increased smoking cessation would yield an estimated 8.1% reduction in cumulative lung cancer mortality by 2050. Our model estimated that the number of screening-eligible individuals would progressively decrease over time, indicating declining benefit of a screening-only programme. Lung cancer screening achieved a greater mortality reduction in earlier years, but was later surpassed by smoking cessation. CONCLUSIONS: Combining smoking cessation programmes with lung cancer screening would provide the most benefit to a population, especially considering the growing proportion of patients ineligible for screening based on current recommendations.

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size: Positive Implications for Future Targeted Screening.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies. METHODS: Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated. RESULTS: A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy. CONCLUSIONS: For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

Financial Hardship Associated With Cancer in the United States: Findings From a Population-Based Sample of Adult Cancer Survivors.

PURPOSE: To estimate the prevalence of financial hardship associated with cancer in the United States and identify characteristics of cancer survivors associated with financial hardship. METHODS: We identified 1,202 adult cancer survivors diagnosed or treated at ≥ 18 years of age from the 2011 Medical Expenditure Panel Survey Experiences With Cancer questionnaire. Material financial hardship was measured by ever (1) borrowing money or going into debt, (2) filing for bankruptcy, (3) being unable to cover one's share of medical care costs, or (4) making other financial sacrifices because of cancer, its treatment, and lasting effects of treatment. Psychological financial hardship was measured as ever worrying about paying large medical bills. We examined factors associated with any material or psychological financial hardship using separate multivariable logistic regression models stratified by age group (18 to 64 and ≥ 65 years). RESULTS: Material financial hardship was more common in cancer survivors age 18 to 64 years than in those ≥ 65 years of age (28.4% v 13.8%; P < .001), as was psychological financial hardship (31.9% v 14.7%, P < .001). In adjusted analyses, cancer survivors age 18 to 64 years who were younger, female, nonwhite, and treated more recently and who had changed employment because of cancer were significantly more likely to report any material financial hardship. Cancer survivors who were uninsured, had lower family income, and were treated more recently were more likely to report psychological financial hardship. Among cancer survivors ≥ 65 years of age, those who were younger were more likely to report any financial hardship. CONCLUSION: Cancer survivors, especially the working-age population, commonly experience material and psychological financial hardship.

Screening for Pancreatic Adenocarcinoma in BRCA2 Mutation Carriers: Results of a Disease Simulation Model.

BACKGROUND: BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy. METHODS: A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast- and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance. FINDINGS: One-time screening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for those with BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with ≥ 3 FDRs, annual screening starting at an earlier age (i.e. 35-40) was optimal. INTERPRETATION: Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings. FUNDING: American Cancer Society - New England Division - Ellison Foundation Research Scholar Grant (RSG-15-129-01-CPHPS).

Five-year risk of interval-invasive second breast cancer.

BACKGROUND: Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. METHODS: We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. RESULTS: The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. CONCLUSIONS: PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans.

Estimating the health and economic burden of cancer among those diagnosed as adolescents and young adults.

Adolescent and young adult cancer survivors-those who were ages 15-39 at their first cancer diagnosis-have important health limitations. These survivors are at risk for higher health care expenditures and lost productivity, compared to adults without a history of cancer. Using Medical Expenditure Panel Survey data, we present nationally representative estimates of the economic burden among people who were diagnosed with cancer in adolescence or young adulthood. Our findings demonstrate that surviving cancer at this age is associated with a substantial economic burden. Compared to adults without a history of cancer, adolescent and young adult cancer survivors had excess annual medical expenditures of $3,170 per person and excess annual productivity losses of $2,250 per person. Multifaceted prevention strategies, including education and sustained intervention programs to ensure access to lifelong risk-based follow-up care, may be effective ways to improve the economic outcomes associated with cancer survivorship in this population.