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Background: Long‐term prognostication is important to inform preventive care in older adults. Existing prediction indices incorporate age and comorbidities. Frailty is another important factor in prognostication. In this project, we aimed at developing life expectancy estimates that incorporate both comorbidities and frailty. Methods: In this retrospective cohort study, we used data from a 5% sample of Medicare beneficiaries with and without history of cancer from Surveillance, Epidemiology, and End Results (SEER) cancer registry areas. We included adults aged 66–95 years who were continuously enrolled in fee‐for‐service Medicare for ≥1 year from 1998 to 2014. Participants were followed for survival until 12/31/2015, death, or disenrollment. Comorbidity (none, low/medium, high) and frailty categories (low, high) were defined using established methods for claims. We estimated 5‐ and 10‐year survival probabilities and median life expectancies by age, sex, comorbidities, and frailty. Results: The study included 479,646 individuals (4,128,316 person‐years), of whom most were women (58.7%). Frailty scores varied widely among participants in the same comorbidity category. In Cox models, both comorbidities and frailty were independent predictors of mortality. Individuals with high comorbidities (HR, 3.24; 95% CI, 3.20–3.28) and low/medium comorbidities (HR, 1.36; 95% CI, 1.34–1.39) had higher risks of death than those with no comorbidities. Compared to low frailty, high frailty was associated with higher risk of death (HR, 1.55; 95% CI, 1.52–1.58). Frailty affected life expectancy estimates in ways relevant to preventive care (i.e., distinguishing <10‐year versus >10‐year life expectancy) in multiple subgroups. Conclusion: Incorporating both comorbidities and frailty may be important in estimating long‐term life expectancies of older adults. Our life expectancy tables can aid clinicians' prognostication and inform simulation models and population health management. [ABSTRACT FROM AUTHOR]

Introduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility.Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations.Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]).Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Rapid access to pancreatic imaging and regular pancreatic surveillance may help identify stage I pancreatic cancer. We investigated recent trends in the stage of newly diagnosed pancreatic ductal adenocarcinoma (PDACs), age at diagnosis, and survival.Methods: Trends in age-adjusted incidence of stage IA PDAC between 2004 and 2016 were determined from the National Cancer Institute's Surveillance, Epidemiology and End Results database. All tests were two-sided.Results: The incidence of stage IA PDAC cases diagnosed increased statistically significantly from 2004 to 2016 (annual percent change = 14.5, 95% confidence interval [CI] = 11.4 to 17.7; P < .001). During the study period, average age at diagnosis for stage IA and IB casesAQ3 declined by 3.5 years (95% CI = 1.2 to 5.9; P = .004) and 5.5 years (95% CI = 3.4 to 7.6; P < .001), whereas average age increased for higher-stage cases (by 0.6 to 1.4 years). Among stage IA cases, the proportion of blacks was smaller (10.2% vs 12.5%), and the proportion of other non-Caucasians was higher compared with higher-stage cases (11.9% vs 8.4%; P < .001). Stage IA cases were more likely to carry insurance (vs Medicaid or none) than higher-stage cases (cases aged younger than 65 years; odds ratio = 2.45, 95% CI = 1.96 to 3.06; P < .001). The 5-year overall survival for stage IA PDAC improved from 44.7% (95% CI = 31.4 to 63.7) in 2004 to 83.7% (95% CI = 78.6% to 89.2%) in 2012; 10-year survival improved from 36.7% (95% CI = 24.1 to 55.8) in 2004 to 49.0% (95% CI = 37.2% to 64.6%) in 2007.Conclusions: In recent years, the proportion of patients diagnosed with stage IA PDAC has increased, their average age at diagnosis has decreased, and their overall survival has improved. These trends may be the result of improved early diagnosis and early detection. [ABSTRACT FROM AUTHOR]

Background: The prevalence of survivors of oropharyngeal cancer (OPC) is increasing due to improved survival for individuals with human papillomavirus (HPV)-related disease. Although elderly survivors of OPC are known to have a high burden of comorbidities, to the authors' knowledge it is unknown how this compares with a similar cohort without a history of cancer.Methods: The current retrospective, cross-sectional study included individuals with a first incident primary diagnosis of OPC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases and matched controls. The baseline prevalence and subsequent incidence of comorbid conditions were identified. The association between comorbidity and overall survival was evaluated.Results: A total of 2497 eligible patients with OPC were matched to 4994 noncancer controls. Baseline comorbidity was higher in cases (Charlson Comorbidity Index >0 for 48.5% of cases vs 35.8% of controls). At 5 years, cases were more likely than controls to develop comorbidities. Survivors of OPC were at high risk (≥20% cumulative prevalence by 5 years) of developing several comorbidities, including cardiovascular diseases, cerebrovascular disease, chronic obstructive pulmonary disease, and tobacco abuse, and were at moderately high risk (10%-19% cumulative prevalence) of developing other conditions including carotid artery occlusive stroke, alcohol abuse, depression, and anxiety. In both cases and controls, the presence of the majority of comorbidities either at the time of diagnosis or during the follow-up period was associated with worse survival.Conclusions: Patients with OPC have a higher comorbidity burden compared with matched controls, both at baseline and during survivorship, the majority of which are associated with decreased survival. Oncologic surveillance of survivors of OPC should include screening for highly prevalent conditions. [ABSTRACT FROM AUTHOR]

Importance: Although neighborhoods are thought to be an important health determinant, evidence for the relationship between neighborhood poverty and health care use is limited, as prior studies have largely used observational data without an experimental design.Objective: To examine whether housing policies that reduce exposure to high-poverty neighborhoods were associated with differences in long-term hospital use among adults and children.Design, Setting, and Participants: Exploratory analysis of the Moving to Opportunity for Fair Housing Demonstration Program, a randomized social experiment conducted in 5 US cities. From 1994 to 1998, 4604 families in public housing were randomized to 1 of 3 groups: a control condition, a traditional Section 8 voucher toward rental costs in the private market, or a voucher that could only be used in low-poverty neighborhoods. Participants were linked to all-payer hospital discharge data (1995 through 2014 or 2015) and Medicaid data (1999 through 2009). The final follow-up date ranged from 11 to 21 years after randomization.Exposures: Receipt of a traditional or low-poverty voucher vs control group.Main Outcomes and Measures: Rates of hospitalizations and hospital days, and hospital spending.Results: Among 4602 eligible individuals randomized as adults, 4072 (88.5%) were linked to health data (mean age, 33 years [SD, 9.0 years]; 98% female; median follow-up, 11 years). There were no significant differences in primary outcomes among adults randomized to receive a voucher compared with the control group (unadjusted hospitalization rate, 14.0 vs 14.7 per 100 person-years, adjusted incidence rate ratio [IRR], 0.95 [95% CI, 0.84-1.08; P = .45]; hospital days, 62.8 vs 67.0 per 100 person-years; IRR, 0.93 [95% CI, 0.77-1.13; P = .46]; yearly spending, $2075 vs $1977; adjusted difference, -$129 [95% CI, -$497 to $239; P = .49]). Among 11 290 eligible individuals randomized as children, 9118 (80.8%) were linked to health data (mean age, 8 years [SD, 4.6 years]; 49% female; median follow-up, 11 years). Receipt of a housing voucher during childhood was significantly associated with lower hospitalization rates (6.3 vs 7.3 per 100 person-years; IRR, 0.85 [95% CI, 0.73-0.99; P = .03]) and yearly inpatient spending ($633 vs $785; adjusted difference, -$143 [95% CI, -$256 to -$31; P = .01]) and no significant difference in hospital days (25.7 vs 28.8 per 100 person-years; IRR, 0.92 [95% CI, 0.77-1.11; P = .41]).Conclusions and Relevance: In this exploratory analysis of a randomized housing voucher intervention, adults who received a housing voucher did not experience significant differences in hospital use or spending. Receipt of a voucher during childhood was significantly associated with lower rates of hospitalization and less inpatient spending during long-term follow-up. [ABSTRACT FROM AUTHOR]

• Cytokine release syndrome (CRS) occurs at day 0 to day +5 in 90% of haploidentical peripheral blood stem cell transplant recipients. • Overall survival in our cohort was 58% at 2 years, because most CRS was mild. • Older patients and those who received radiation therapy are more prone to severe CRS. • Nonrelapse mortality was 38% at 6 months among patients with severe CRS. Inflammatory cytokines released by activated lymphocytes and innate cells in the context of cellular therapy can cause fever, vasodilatation, and end-organ damage, collectively known as cytokine release syndrome (CRS). CRS can occur after allogeneic blood or marrow transplantation, but is especially prevalent after HLA-haploidentical (haplo) peripheral blood transplantation (PBT). We reviewed charts of all patients who underwent haplo-PBT between October 1, 2013, and September 1, 2017 and graded CRS in these patients. A total of 146 consecutive patients who underwent related haplo-PBT were analyzed. CRS occurred in 130 patients (89%), with most cases of mild severity (grade 0 to 2). Severe CRS (grade 3 to 5) occurred in 25 patients (17%). In this group with severe CRS, 13 patients had encephalopathy, 12 required hemodialysis, and 11 were intubated. Death from the immediate complications of CRS occurred in 6 patients (24% of the severe CRS group and 4% of the entire haplo-PBT cohort). The cumulative probability of nonrelapse mortality (NRM) was 38% at 6 months for the patients with severe CRS and 8% (121 of 146) in patients without severe CRS. In conclusion, CRS occurs in nearly 90% of haplo-PBTs. Older haplo-PBT recipients (odds ratio [OR], 2.4; 95% confidence interval [CI],.83 to 6.75; P =.11) and those with a history of radiation therapy (OR, 3.85; 95% CI, 1.32 to 11.24; P =.01) are at increased risk of developing severe CRS. Although most recipients of haplo-PBT develop CRS, <20% experience severe complications. The development of severe CRS is associated with a significantly increased risk of NRM. [ABSTRACT FROM AUTHOR]

Background: The increasing incidence of human papillomavirus (HPV)-related head and neck cancer (HNC) has led to the increasing prevalence of survivors, yet to the best of the authors' knowledge the prevalence of comorbidities during the survivorship period and their effects on survival are relatively unknown.Methods: In this retrospective cross-sectional study, individuals with a first incident primary diagnosis of HNC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases were included in the analysis and classified as patients with HPV-related or HPV-unrelated HNC. The presence of 30 comorbid conditions of interest was identified. Associations between comorbidity and treatment group as well as overall survival were evaluated.Results: The study population consisted of 8025 patients with HPV-unrelated HNC and 2499 patients with HPV-related HNC. Hypertension, congestive heart failure, cerebrovascular disease, and chronic obstructive pulmonary disease all were found to be highly prevalent at the time of the cancer diagnosis and increased over time for both groups. These comorbidities were found at significantly lower rates in the HPV-related HNC population, yet were associated with an increased risk of death in both groups. The probabilities of developing cancer-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in both groups after treatment but were more likely in patients with HPV-related HNC. In both groups of patients, the presence of each comorbidity either at the time of diagnosis or during survivorship was associated with a significantly increased risk of death.Conclusions: There is a large burden of comorbidities in both patients with HPV-related and HPV-unrelated HNC, both of which are associated with decreased survival. Oncologic surveillance should not be limited to the evaluation of disease status, but also should include screening for the highly prevalent conditions associated with the risk of death. [ABSTRACT FROM AUTHOR]

Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype. Loss of heterozygosity analysis was performed for patients with acute myeloid leukemia (AML) whose first allograft was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to 2950) days. The median overall survival (OS) in the cohort is 928 days (95% confidence interval [CI], 602 to not reached [NR]); median event-free survival (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95% CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552 days (95% CI, 376 to 2950+) in the group who underwent transplantation with a second allograft that did not harbor a new mismatched haplotype, while it was not reached in the group whose allograft contained a new mismatched haplotype (hazard ratio [HR], .36; 95% CI, .14 to .9; P  = .02). EFS was also longer in the group who received an allograft containing a new mismatched haplotype, (NR versus 401 days; HR, .50; 95% CI, .22 to 1.14; P  = .09). Although the allograft for this patient's second BMT contained a new mismatched haplotype, AML nevertheless relapsed a second time. Second BMTs are feasible and provide a reasonable chance of long-term survival. An allograft with a new mismatched haplotype may improve outcomes after second BMTs for relapsed hematologic malignancies. [ABSTRACT FROM AUTHOR]

Objectives To compare the agreement and rates of cancer screening using four prognostic tools that require different types of clinical information. Design Observational retrospective cohort study. Setting 2009 and 2010 waves of the Medicare Current Beneficiary Survey. Participants Adults aged 66-90 with survey and claims data ( N = 9,469). Measurements Agreement between four indices predicting short-term (4-5 years) and long-term (9-10 years) survival; self-reported breast and prostate cancer screening. Results Agreement between the four prognostic tools was high. Pearson correlation coefficients ranged from 0.63 to 0.90 for short-term survival and 0.68 to 0.94 for long-term survival. When defining limited short-term life expectancy as less than 25% chance of surviving 4 or 5 years, all four tools agreed in 96.4% of the sample. All four tools agreed in their placement of participants into limited or not-limited long-term life expectancy in 77.1% of participants (<25% chance of surviving 9 or 10 years). Rates of cancer screening were similarly high in individuals with limited long-term life expectancy regardless of the tool used: greater than 31% for mammographic screening in women and greater than 69% for prostate cancer screening. Conclusion There is substantial agreement among different prognostic tools for short- and long-term survival in Medicare beneficiaries. The high rates of cancer screening of individuals with limited life expectancy suggest the importance of incorporating tools into clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: The incidence of oropharyngeal cancer (OPC) and a subset of oral cavity cancer (OCC) is increasing in the United States. To the authors' knowledge, the presumed growing prevalence of survivors of OPC and OCC has not been investigated to date.Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results data (1975-2012) estimated changes in incidence, 5-year cause-specific survival, and prevalence for OPC and OCC. Changes in incidence, cause-specific survival and prevalence were estimated by linear regression and expressed as the percentage change (B). Differences in incidence trends over time were determined by joinpoint analysis.Results: The incidence of OPC increased by 62.6% from 1975 through 2012. Notable increases in OPC incidence were observed among men, white individuals, and those of younger ages. The 5-year survival for OPC increased significantly for all sexes, races, and individuals aged >30 years, with white individuals and males experiencing the largest increase in survival. By contrast, the incidence of OCC declined by 22.3% during the same time period. OCC incidence decreased across all groups but increased among individuals aged 30 to 39 years. Significant increases in survival were observed for OCC, except for those who were female, black, and aged <40 years. The prevalence of survivors of OPC increased from 2000 to 2012 (B, 115.1 per 100,000 individuals per year; P<.0001), whereas the prevalence of survivors of OCC significantly decreased (B, -15.8 per 100,000 individuals per year; P<.0001).Conclusions: The prevalence of survivors of OPC is increasing, whereas the prevalence of survivors of OCC is declining. These data portend significant implications for long-term care planning for survivors of OPC and OCC. Cancer 2016;122:1380-1387. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: Although pancreatic ductal adenocarcinoma is considered a rapidly progressive disease, mathematical models estimate that it takes many years for an initiating pancreatic cancer cell to grow into an advanced stage cancer. In order to estimate the time it takes for a pancreatic cancer to progress through different tumor, node, metastasis (TNM) stages, we compared the mean age of patients with pancreatic cancers of different sizes and stages. Design: Patient age, tumour size, stage and demographic information were analysed for 13 131 patients with pancreatic ductal adenocarcinoma entered into the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. Multiple linear regression models for age were generated, adjusting for patient ethnicity, gender, tumour location and neoplastic grades. Results: African-American ethnicity and male gender were associated with an earlier age at diagnosis. Patients with stage I cancers (mean age 64.8 years) were on average 1.3 adjusted years younger at diagnosis than those with stage IV cancers (p=0.001). Among patients without distant metastases, those with T1 stage cancers were on average 1.06 and 1.19 adjusted years younger, respectively, than patients with T3 or T4 cancers (p=0.03 for both). Among patients with stage IIB cancers, those with T1/T2 cancers were 0.79 adjusted years younger than those with T3 cancers (p=0.06). There was no significant difference in the mean adjusted age of patients with stage IA versus stage IB cancers. Conclusions: These results are consistent with the hypothesis that once pancreatic ductal adenocarcinomas become detectable clinically progression from low-stage to advanced-stage disease is rapid. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported outcomes (PROs) are used increasingly for individual patient management. Identifying which PRO scores require a clinician's attention is an ongoing challenge. Previous research used a needs assessment to identify EORTC-QLQ-C30 cutoff scores representing unmet needs. This analysis attempted to replicate the previous findings in a new and larger sample.Methods: This analysis used data from 408 Japanese ambulatory breast cancer patients who completed the QLQ-C30 and Supportive Care Needs Survey-Short Form-34 (SCNS-SF34). Applying the methods used previously, SCNS-SF34 item/domain scores were dichotomized as no versus some unmet need. We calculated area under the receiver operating characteristic curve (AUC) to evaluate QLQ-C30 scores' ability to discriminate between patients with no versus some unmet need based on SCNS-SF34 items/domains. For QLQ-C30 domains with AUC ≥ 0.70, we calculated the sensitivity, specificity, and predictive value of various cutoffs for identifying unmet needs. We hypothesized that compared to our original analysis, (1) the same six QLQ-C30 domains would have AUC ≥ 0.70, (2) the same SCNS-SF34 items would be best discriminated by QLQ-C30 scores, and (3) the sensitivity and specificity of our original cutoff scores would be supported.Results: The findings from our original analysis were supported. The same six domains with AUC ≥ 0.70 in the original analysis had AUC ≥ 0.70 in this new sample, and the same SCNS-SF34 item was best discriminated by QLQ-C30 scores. Cutoff scores were identified with sensitivity ≥0.84 and specificity ≥0.54.Conclusion: Given these findings' concordance with our previous analysis, these QLQ-C30 cutoffs could be implemented in clinical practice and their usefulness evaluated. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported outcomes (PROs) are used increasingly for individual patient management. Identifying which PRO scores require a clinician’s attention is an ongoing challenge. Previous research used a needs assessment to identify EORTC-QLQ-C30 cutoff scores representing unmet needs. This analysis attempted to replicate the previous findings in a new and larger sample. Methods: This analysis used data from 408 Japanese ambulatory breast cancer patients who completed the QLQ-C30 and Supportive Care Needs Survey-Short Form-34 (SCNS-SF34). Applying the methods used previously, SCNS-SF34 item/domain scores were dichotomized as no versus some unmet need. We calculated area under the receiver operating characteristic curve (AUC) to evaluate QLQ-C30 scores’ ability to discriminate between patients with no versus some unmet need based on SCNS-SF34 items/domains. For QLQ-C30 domains with AUC ≥ 0.70, we calculated the sensitivity, specificity, and predictive value of various cutoffs for identifying unmet needs. We hypothesized that compared to our original analysis, (1) the same six QLQ-C30 domains would have AUC ≥ 0.70, (2) the same SCNS-SF34 items would be best discriminated by QLQ-C30 scores, and (3) the sensitivity and specificity of our original cutoff scores would be supported. Results: The findings from our original analysis were supported. The same six domains with AUC ≥ 0.70 in the original analysis had AUC ≥ 0.70 in this new sample, and the same SCNS-SF34 item was best discriminated by QLQ-C30 scores. Cutoff scores were identified with sensitivity ≥0.84 and specificity ≥0.54. Conclusion: Given these findings’ concordance with our previous analysis, these QLQ-C30 cutoffs could be implemented in clinical practice and their usefulness evaluated. [ABSTRACT FROM AUTHOR]

Background The PatientViewpoint website collects patient-reported outcomes and links them with the electronic health record to aid patient management. This pilot test evaluated PatientViewpoint's use, usefulness, and acceptability to patients and clinicians. Methods This was a single-arm prospective study that enrolled breast and prostate cancer patients undergoing treatment and the clinicians who managed them. Patients completed patient-reported outcomes every 2 weeks, and clinicians could access the results for patient visits. Scores that were poor relative to norms or substantially worse than the previous assessment were highlighted. After three on-study visits, we assessed patient and clinician perspectives on PatientViewpoint using close-ended and open-ended questions. Results Eleven out of 12 eligible clinicians (92%) and 52/76 eligible patients (68%) enrolled. Patients completed a median of 71% of assigned questionnaires; clinicians reported using the information for 79% of patients, most commonly as a source of additional information (51%). At the median, score reports identified three potential issues, of which 1 was discussed during the visit. Patients reported the system was easy to use (92%), useful (70%), aided recall of symptoms/side effects (72%), helped them feel more in control of their care (60%), improved discussions with their provider (49%), and improved care quality (39%). Patients and clinicians desired more information on score interpretation and minor adjustments to site navigation. Conclusions These results support the feasibility and value of PatientViewpoint. An ongoing study is using a continuous quality improvement approach to further refine PatientViewpoint. Future studies will evaluate its impact on patient care and outcomes. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A barrier to using HRQOL questionnaires for individual patient management is knowing what score represents a problem deserving attention. We explored using needs assessments to identify HRQOL scores associated with patient-reported unmet needs. This cross-sectional study included 117 cancer patients (mean age 61 years; 51% men; 77% white) who completed the Supportive Care Needs Survey (SCNS) and EORTC QLQ-C30. SCNS scores were dichotomized as “no unmet need” versus “some unmet need” and served as an external criterion for identifying problem scores. We evaluated the discriminative ability of QLQ-C30 scores using receiver operating characteristic (ROC) analysis. Domains with an area under the ROC curve (AUC) ≥ .70 were examined further to determine how well QLQ-C30 scores predicted presence/absence of unmet need. We found AUCs ≥ .70 for 6 of 14 EORTC domains: physical, emotional, role, global QOL, pain, fatigue. All 6 domains had sensitivity ≥ .85 and specificity ≥ .50. EORTC domains that closely matched the content of SCNS item(s) were more likely to have AUCs ≥ .70. The appropriate cut-off depends on the relative importance of false positives and false negatives. Needs assessments can identify HRQOL scores requiring clinicians’ attention. Future research should confirm these findings using other HRQOL questionnaires and needs assessments. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the use of continuous oxygen in nonhypoxemic emphysema patients. The study made use of former smokers with severe emphysema and are deemed to be candidates for lung volume reduction surgery. Oxygen therapy was prescribed by the primary care physician and by National Emphysema Treatment Trial (NETT) physician. Findings on this study were obtained such as the use of oxygen in normoxic patients identifies a high risk of emphysema patients.

We would like to thank Dr. Braillon for his response to our article.[1] He has thoughtfully highlighted several important issues. This alarming trend may reflect missed opportunities for patient counseling, which is supported by the findings of 2 large studies that surveyed cancer survivors. [Extracted from the article]

Advances in biomedical research require a robust physician scientist workforce. Despite being equally successful at securing early career awards from the NIH as men, women MD-PhD physician scientists are less likely to serve as principal investigators on mid- and later careers awards. Here, we discuss the causes of gender disparities in academic medicine, the implications of losing highly trained women physician scientists, and the institutional and systemic changes needed to sustain this pool of talented investigators. [ABSTRACT FROM AUTHOR]

Background: Survivorship care plans seek to improve the transition to survivorship, but the required resources present implementation barriers. This randomized controlled trial aimed to identify the simplest, most effective approach for survivorship care planning.Methods: Stage 1-3 breast, colorectal, and prostate cancer patients aged 21 years or older completing treatment were recruited from an urban-academic and rural-community cancer center. Participants were randomly assigned, stratified by recruitment site and cancer type 1:1:1 to a mailed plan, plan delivered during a 1-time transition visit, or plan delivered during a transition visit plus 6-month follow-up visit. Health service use data were collected from participants and medical records for 18 months. The primary outcome, receipt of all plan-recommended care, was compared across intervention arms using logistic regression adjusting for cancer type and recruitment site, with P less than .05 considered statistically significant.Results: Of 378 participants randomly assigned, 159 (42.1%) were breast, 142 (37.6%) prostate, and 77 (20.4%) colorectal cancer survivors; 207 (54.8%) from the academic site and 171 (45.2%) from the community site; 316 were analyzable for the primary outcome. There was no difference across arms in the proportion of participants receiving all plan-recommended care: 45.2% mail, 50.5% 1-visit, 42.7% 2-visit (2-sided P = .60). Adherence by cancer type for mail, 1-visit, and 2-visit, respectively, was 52.2%, 53.3%, and 40.0% for breast cancer; 48.6%, 64.1%, and 57.1% for prostate cancer; and 23.8%, 19.0%, and 26.1% for colorectal cancer. There were no statistically significant interactions by recruitment site or cancer type.Conclusions: This study did not find differences in receipt of recommended follow-up care by plan delivery approach. Feasibility and other factors may determine the best approach for survivorship care planning. [ABSTRACT FROM AUTHOR]

Background/objectives: To assess whether vitamin D supplementation prevents specific fall subtypes and sequelae (e.g., fracture). Design Secondary analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You)—a response‐adaptive, randomized clinical trial. Setting: Two community‐based research units. Participants: Six hundred and eighty‐eight participants ≥70 years old with elevated fall risk and baseline serum 25‐hydroxyvitamin D levels of 10–29 ng/ml. Intervention: 200 IU/day (control), 1000 IU/day, 2000 IU/day, or 4000 IU/day of vitamin D3. Measurements Outcomes included repeat falls and falls that were consequential, were injurious, resulted in emergency care, resulted in fracture, and occurred either indoors or outdoors. Results: After adjustment for multiple comparisons, the risk of fall‐related fracture was greater in the pooled higher doses (≥1000 IU/day) group compared with the control (hazard ratio [HR] = 2.66; 95% confidence interval [CI]:1.18–6.00). Although not statistically significant after multiple comparisons adjustment, time to first outdoor fall appeared to differ between the four dose groups (unadjusted p for overall difference = 0.013; adjusted p = 0.222), with risk of a first‐time outdoor fall 39% lower in the 1000 IU/day group (HR = 0.61; 95% CI: 0.38–0.97; unadjusted p = 0.036; adjusted p = 0.222) and 40% lower in the 2000 IU/day group (HR = 0.60; 95%CI 0.38–0.97; p = 0.037; adjusted p = 0.222), each versus control. Conclusion: Vitamin D supplementation doses ≥1000 IU/day might have differential effects on fall risk based on fall location and fracture risk, with the most robust finding that vitamin D doses between 1000 and 4000 IU/day might increase the risk of first time falls with fractures. Replication is warranted, given the possibility of type 1 error. [ABSTRACT FROM AUTHOR]

Neighborhood environments are increasingly thought to affect emergency department (ED) use. However, because people decide where to live based on a range of factors, it can be challenging to identify the causal impact of living in higher-poverty neighborhoods on increased rates of ED visits. Our study leveraged the Moving to Opportunity for Fair Housing Demonstration Program, a social experiment beginning in 1994 that randomly assigned approximately 4,600 households that received federal housing assistance to different neighborhood conditions. We linked program participants in four states with an average of twelve years of administrative data on ED use (up to twenty-one years after randomization). Contrary to our expectations, we did not find a consistently significant connection between neighborhood poverty and overall ED use during this follow-up period. This result was observed for both adults and people who were children at the time of randomization, as well as for various classifications of ED visits. The findings can help direct future research that seeks to clarify the relationship between neighborhood environments and health care use. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how often women with a history of breast cancer who are taking hormone therapy (HT) filled prescriptions for topical estrogens and whether this frequency varied over time and by type of HT used.Methods: We performed a retrospective cohort study using medical and outpatient drug claims from a large commercial claims database for the years 2010-2015. Women younger than age 65 years taking HT for breast cancer were classified as users of 1) tamoxifen only, 2) aromatase inhibitor(s) only, or 3) any other or multiple HTs. Our outcome variable was filling a prescription for topical estrogen in a given year. We used multivariable logistic regression models estimated with generalized estimating equations to determine whether the fill rate varied over time and by HT category adjusting for age, receipt of surgical or radiation treatment, types of outpatient health care provider visits, and comorbidities.Results: We identified 352,118 records from 176,012 unique patients (mean age 54.3 years, range 18-64 years) who met eligibility criteria. Aromatase inhibitors were used more commonly (56.0% of patient-years) than tamoxifen (38.8%). Overall, 3.0% (range 2.9-3.1%) of women filled any topical estrogen prescription in a given calendar year. More than half of filled topical estrogen prescriptions were for tablets (57.0%) with the remainder for creams (25.8%) and rings (17.3%). In adjusted analyses, the fill rate for women taking tamoxifen was significantly less (2.4%; 95% CI 2.3-2.5%) than for women taking aromatase inhibitors (3.3%; 95% CI 3.2-3.4%). There was a small but statistically significant increase in fill rates across years (odds ratio 1.03, 95% CI 1.02-1.04).Conclusion: A small proportion of women with a history of breast cancer who were taking HT filled a topical estrogen prescription, with significant differences by type of HT. More evidence is needed to inform national guidelines regarding safety and appropriate use of topical estrogens in this patient population. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To identify predictive signs and symptoms occurring in hospitalized adults with hematologic malignancies with intracranial hemorrhage (IH). SAMPLE & SETTING: In a National Cancer Institute (NCI)--designated comprehensive cancer center, a retrospective matched case-control design included adult inpatients with hematologic malignancies with (n = 39) and without (n = 39) IH. METHODS & VARIABLES: Conditional logistic regression, t test, and Fisher's exact tests were used to assess increased risks for IH and the development of a prognostic nomogram with signs, symptoms, and laboratory values relevant to IH. RESULTS: Composite outcomes for signs, symptoms, and laboratory values were included in a prognostic nomogram that had good discriminative ability to predict IH, with a bootstrap corrected concordance index of 0.766 (95% confidence interval [0.657, 0.866]) and good calibration. Prognostic nomogram predicted patients with prolonged activated partial thromboplastin time (APTT) (greater than 30.6), headache, and systolic blood pressure (SBP) of 140 or greater were more likely to have IH. IMPLICATIONS FOR NURSING: Nurses should recognize that patients with the combination of prolonged APTT, SBP of 140 or greater, and headache are more likely to have IH. [ABSTRACT FROM AUTHOR]

Background: Survivorship care plans (SCPs) communicate cancer‐related information from oncology providers to patients and primary care providers. SCPs may limit overuse testing by specifying necessary follow‐up care. From a randomized, controlled trial of SCP delivery, we examined whether cancer‐related tests not specified in SCPs, but conducted after SCP receipt, were appropriate or consistent with overuse. Methods: Survivors of breast, colorectal, or prostate cancer treated at urban‐academic or rural‐community health systems were randomized to one of three SCP delivery arms. Tests during 18 months after SCP receipt were classified as consistent with overuse if they were (1) not included in SCPs and (2) on a guideline‐based predetermined list of "not recommended surveillance." After chart abstraction, physicians performed review and adjudication of potential overuse. Descriptive analyses were conducted of tests consistent with overuse. Negative binomial regression models determined if testing consistent with overuse differed across study arms. Results: Among 316 patients (137 breast, 67 colorectal, 112 prostate), 140 individual tests were identified as potential overuse. Upon review, 98 were deemed to be consistent with overuse: 78 tumor markers and 20 imaging tests. The majority of overuse testing was breast cancer‐related (95%). Across sites, 27 patients (9%) received ≥1 test consistent with overuse; most were breast cancer patients (22/27). Exploratory analyses of overuse test frequency by study arm showed no significant difference. Conclusions: This analysis identified practice patterns consistent with overuse of surveillance testing and can inform efforts to improve guideline‐concordant care. Future interventions may include individual practice patterns and provider education. [ABSTRACT FROM AUTHOR]

Background: Prospective studies have identified obstructive sleep apnea (OSA) as a risk factor for increased overall cancer incidence and mortality. The potential role of OSA in the risk or progression of specific cancers is not well known. We hypothesized that pathological differences in pancreatic cancers from OSA cases compared to non-OSA cases would implicate OSA in pancreatic cancer progression. Methods: We reviewed the medical records of 1031 patients who underwent surgical resection without neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2003 and 2014 and compared the TNM classification of their cancer and their overall survival by patient OSA status. Results: OSA cases were significantly more likely than non-OSA cases to have lymph node-negative tumors (37.7% vs. 21.8%, p = 0.004). Differences in the prevalence of nodal involvement of OSA vs. non-OSA cases were not associated with differences in other pathological characteristics such as tumor size, tumor location, resection margin status, vascular or perineural invasion, or other comorbidities more common to OSA cases (BMI, smoking, diabetes). A logistic regression model found that a diagnosis of OSA was an independent predictor of lymph node status (hazard ratio, 0.051, p = 0.038). Patients with OSA had similar overall survival compared to those without OSA (HR, 0.89, (0.65–1.24), p = 0.41). Conclusion: The observed pathological differences between OSA-associated and non-OSA-associated pancreatic cancers supports the hypothesis that OSA can influence the pathologic features of pancreatic ductal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Orthostatic hypotension (OH) based on a change from seated‐to‐standing blood pressure (BP) is often used interchangeably with supine‐to‐standing BP. Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a randomized trial of vitamin D3 supplementation and fall in adults aged ≥70 years at high risk of falls. OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mmHg, measured at pre‐randomization, 3‐, 12‐, and 24‐month visits with each of 2 protocols: seated‐to‐standing and supine‐to‐standing. Participants were asked about orthostatic symptoms, and falls were ascertained via daily fall calendar, ad hoc reporting, and scheduled interviews. Results: Among 534 participants with 993 paired supine and seated assessments (mean age 76 ± 5 years, 42% women, 18% Black), mean baseline BP was 130 ± 19/68 ± 11 mmHg; 62% had a history of high BP or hypertension. Mean BP increased 3.5 (SE, 0.4)/2.6 (SE, 0.2) mmHg from sitting to standing, but decreased with supine to standing (mean change: −3.7 [SE, 0.5]/−0.8 [SE, 0.3] mmHg; P‐value < 0.001). OH was detected in 2.1% (SE, 0.5) of seated versus 15.0% (SE, 1.4) of supine assessments (P < 0.001). While supine and seated OH were not associated with falls (HR: 1.55 [0.95, 2.52] vs 0.69 [0.30, 1.58]), supine systolic OH was associated with higher fall risk (HR: 1.77 [1.02, 3.05]). Supine OH was associated with self‐reported fainting, blacking out, seeing spots and room spinning in the prior month (P‐values < 0.03), while sitting OH was not associated with any symptoms (P‐values ≥ 0.40). Conclusion: Supine OH was more frequent, associated with orthostatic symptoms, and potentially more predictive of falls than seated OH. [ABSTRACT FROM AUTHOR]

Background: Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time.Methods: A retrospective analysis was performed on 711 adult AML patients enrolling in 45 phase I clinical trials supported by the Cancer Therapy Evaluation Program of the National Cancer Institute from 1986 to 2009. Changes in ORR and mortality rates for patients enrolled in 1986 to 1990, 1991 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009 were estimated with multivariable logistic regression models. All statistical tests were two-sided.Results: There was a statistically significant increase in AML patients enrolling in phase I clinical trials over time (1986 to 1990: n = 61; 2006 to 2009: n = 256; P = .03). The ORR for the entire cohort was 15.4% (1986 to 1990: 8.9%, 1991 to 1995: 21.1%; 1996 to 2000: 7.0%; 2001 to 2005: 10.0%; 2006 to 2009: 22.6%), and it statistically significantly improved over time (P < .001). There was a statistically significant improvement in ORRs with novel agents in combination vs single agents (ORR = 22.8% vs 4.7%, respectively, odds ratio = 5.95, 95% confidence interval = 3.22 to 11.9, P < .001). The 60-day mortality rate for the entire cohort was 22.6%, but it statistically significantly improved over time (P = .009).Conclusions: There has been an encouraging increase in AML patients enrolling in phase I clinical studies over time. The improvement in ORRs appears to be partly because of the increase in combination trials and the inclusion of previously untreated poor-risk AML. Continued enrollment of AML patients in early phase clinical trials is vital for drug development and improvement in therapeutic outcomes. [ABSTRACT FROM AUTHOR]

• Adjuvant interferon-α/GM-CSF and K562/G-CSF vaccine were safe with TKIs. • Patients more frequently discontinued interferon-α/GM-CSF due to side effects. • Adjuvant interferon-α/GM-CSF more frequently led to undetectable BCR-ABL PCR. • 36.4 % of patients sustained treatment-free remission after interferon-α/GM-CSF. Chronic myeloid leukemia (CP-CML) patients can achieve undetectable minimal residual disease (UMRD) and discontinue tyrosine kinase inhibitors (TKIs). Cellular immunity plays an important role in CML disease control. We conducted a randomized, non-blinded phase II trial of adjuvant immunotherapy with TKIs to facilitate TKI discontinuation. TKI-treated patients with CP-CML were randomized to receive the K562/GM-CSF vaccine (vaccine) OR Interferon-α + Sargramostim (IFN). If UMRD was achieved, then all treatment was stopped. Patients who did not achieve UMRD within one year, had a molecular relapse, or discontinued therapy for toxicity could crossover. Thirty-four patients were randomized to IFN (n = 18) or vaccine (n = 16), and 21 patients crossed over (IFN⟶vaccine: n = 9, vaccine⟶IFN, n = 12). TKIs at enrollment included imatinib (n = 31), nilotinib (n = 2), and dasatinib (n = 1). No patients discontinued vaccine due to side effects, while 33 % of IFN-treated patients discontinued treatment. More patients randomized to IFN (47.4 %, 95 % CI: 16.7–66.7 %) versus vaccine (25.0 %, 95 % CI: 0.5–43.5 %) achieved UMRD within one year. Seven patients randomized to IFN discontinued treatment with 28.6 % (95 % CI: 8.9–92.2 %) sustaining treatment-free remission (TFR) at 1 year, while three patients randomized to vaccine discontinued treatment with none sustaining TFR. Including crossover, there was a cumulative discontinuation success rate of 36.4 % (95 % CI: 16.6 %–79.5 %) after adjuvant IFN. Patients who sustained TFR received a median of 29 months of imatinib prior to discontinuation. Adjuvant IFN led to durable TFRs with limited prior TKI exposure with comparable success to prior discontinuation trials, but many patients stopped IFN early. [ABSTRACT FROM AUTHOR]

The article provides information on a study which explored how initial treatment choice affects both the short-term and long-term costs for clinically localized prostate cancer. A background on the prevalence of prostate cancer in the U.S. is offered. The research authors followed up men diagnosed with prostate cancer in 2000 from one month prior to diagnosis to five years postdiagnosis or until death. Data analyzed were from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Findings of the study are discussed.

Although patients’ function, symptoms, and supportive care needs are obviously related, a better understanding of these relationships could improve patient management. In this cross-sectional, observational study, 117 cancer patients completed the Supportive Care Needs Survey-34 and EORTC-QLQ-C30. Each symptom and function domain from the EORTC-QLQ-C30 was dichotomized (high vs. low) using a cut-off of reference sample mean scores. Each need domain was dichotomized using a cut-off of an average score representing an unmet need. We explored within-patient patterns of function, symptom, and need domains using latent class analysis. Based on these patterns, patients were categorized as high versus low function; high versus low symptom; and high versus low need. We examined the concordance between categorizations of patients’ function, symptoms, and needs. The categorizations of function, symptoms, and needs were concordant for 66 patients (56%). Among patients with deficits in at least one area ( n = 68), categorizations for 51 patients (75%) were discordant. About 50% of patients have similar classifications of their level of function, symptoms, and needs, but discordance was common among patients with deficits in at least one area, emphasizing the importance of assessing all of these outcomes as part of patient evaluations. [ABSTRACT FROM AUTHOR]

Background: Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences.Objective: To compare the effects of 4 doses of vitamin D3 supplements on falls.Design: 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333).Setting: 2 community-based research units.Participants: 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L.Intervention: 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose.Measurements: Time to first fall or death over 2 years (primary outcome).Results: During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]).Limitations: The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached.Conclusion: In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher.Primary Funding Source: National Institute on Aging. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported outcome (PRO) data from clinical trials can promote valuable patient-clinician communication and aid the decision-making process regarding treatment options. Despite these benefits, both patients and doctors face challenges in interpreting PRO scores. The purpose of this study was to identify best practices for presenting PRO results expressed as proportions of patients with changes from baseline (improved/stable/worsened) for use in patient educational materials and decision aids.Methods: We electronically surveyed adult cancer patients/survivors, oncology clinicians, and PRO researchers, and conducted one-on-one cognitive interviews with patients/survivors and clinicians. Participants saw clinical trial data comparing two treatments as proportions changed using three different formats: pie charts, bar graphs, icon arrays. Interpretation accuracy, clarity, and format preference were analyzed quantitatively and online survey comments and interviews, qualitatively.Results: The internet sample included 629 patients, 139 clinicians, and 249 researchers; 10 patients and 5 clinicians completed interviews. Bar graphs were less accurately interpreted than pie charts (OR 0.39; p < .0001) and icon arrays (OR 0.47; p < .0001). Bar graphs and icon arrays were less likely to be rated clear than pie charts (OR 0.37 and OR 0.18; both p < .0001). Qualitative data informed interpretation of these findings.Conclusions: For communicating PROs as proportions changed in patient educational materials and decision aids, these results support the use of pie charts. [ABSTRACT FROM AUTHOR]

Background: In the USA, a quarter of elderly patients do not receive any treatment for regional gastric cancer, which results in poorer outcomes. We sought to identify factors associated with undertreatment of regional gastric cancer in this population, as well as to assess overall survival in the undertreated population.Methods: Elderly patients (aged ≥ 65 years) diagnosed with regional gastric cancer between 2001 and 2009 were identified from the Surveillance Epidemiology and End Results (SEER)-Medicare linked databases. Treatment was defined as receiving any medical or surgical therapy for gastric cancer. Logistic regression analysis was used to identify factors associated with failure to receive treatment. Overall survival was analyzed using the Kaplan-Meier method and Cox proportional hazard model.Results: Of 5972 patients with regional gastric cancer, 1586 (26.5%) received no treatment. Median age was 78 years; 56.1% of patients were men. On multivariable analysis, the factors strongly associated with lack of therapy were age ≥ 80 years, black race, lower education level, and diagnosis before 2007. As expected, patients who received therapy had better overall survival (log-rank test, p < 0.001). Specifically, median survival and 5-year survival were 16.5 months and 20.5% for treated patients, compared with 9.1 months and 19.0% for untreated patients.Conclusions: Elderly patients with gastric cancer have better overall 5-year survival after receiving treatment for their cancer. Disparities in the use of treatment for curable cancers are associated with older age, black race, lower educational level, and diagnosis before 2007. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults, but there is limited information on survivors' quality of life (QOL) after remission. Objective: We piloted a survey exploring patient-reported outcomes for people with AML in first complete remission (CR1) to determine whether patients felt the survey is relevant to their well-being and to summarize patient characteristics. Design/Measurements: Cross-sectional survey of a convenience sample of AML patients in CR1 assessing QOL and functioning (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30 v 3.0), well-being (QOL-cancer survivor [QOL-CS]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), and anxiety and depression (hospital anxiety and depression scale [HADS]). The survey contained five open-ended questions. Results: Eighteen patients completed the survey. Most felt it was completely or mostly relevant (88.8%) in describing their QOL. Participants scored well on the EORTC QLQ-C30, fatigue being the most common symptom (83%).The FACIT-Fatigue mean score was 28.7 and median score was 33.5 (normal ≥30). Two scored in the abnormal range for anxiety and one for depression on the HADS. On the QOL-CS, participants scored more than 6 out of 10 in most domains, except the subscales of distress and fear. Conclusions: The survey content and length were appropriate. Patients reported ongoing fatigue, fears of future test results, getting a second cancer, and recurrence of cancer. Survivors experience ongoing symptoms, highlighting the importance of providers performing ongoing symptom and needs assessments. [ABSTRACT FROM AUTHOR]

Purpose Cytosine arabinoside (AraC) remains the backbone of most treatment regimens for acute myeloid leukemia (AML). Incorporation of AraC into DNA activates checkpoint kinase 1 (Chk1), leading to cell-cycle arrest and diminished AraC cytotoxicity, which can be reversed by the selective Chk1 inhibitor MK-8776. Building on a Phase I trial, we conducted a phase II trial comparing timed sequential AraC with or without MK-8776. Methods Patients with relapsed or primary refractory AML were randomized 1:1 to receive either AraC with MK-8776 (Arm A); or AraC alone (Arm B). Results 32 patients were treated: 14 assigned to Arm A and 18 to Arm B. There were 5 (36%) complete responses (CR/CRi) and 1 (7%) partial response (PR) in Arm A, and 8 (44%) CR/CRis and 1 (6%) PR in Arm B. Median survival did not differ significantly between the two groups (5.9 months in Arm A vs. 4.5 months in Arm B). MK-8776 led to a robust increase in DNA damage in circulating leukemic blasts as measured by increased γ-H2AX (16.9% ± 6.1% prior and 36.4% ± 6.8% at one hour after MK-8776 infusion, p = 0.016). Conclusion Response rates and survival were similar between the two groups in spite of evidence that MK-8776 augmented DNA damage in circulating leukemic blasts. Better than expected results in the control arm using timed sequential AraC and truncated patient enrollment may have limited the ability to detect clinical benefit from the combination. [ABSTRACT FROM AUTHOR]

Patients with short telomere syndromes (STS) are predisposed to developing cancer, believed to stem from chromosome instability in neoplastic cells. We tested this hypothesis in a large cohort assembled over the last 20 years. We found patients with STS are only predisposed to squamous cell carcinoma of the head and neck, anus, or skin, a spectrum reminiscent of cancers seen in patients with immunodeficiency. Whole-genome sequencing showed no increase in chromosome instability, such as translocations or chromothripsis. Moreover, STS-associated cancers acquired telomere maintenance mechanisms, including telomerase reverse transcriptase (TERT) promoter mutations. A detailed study of the immune status of patients with STS revealed a striking T cell immunodeficiency at the time of cancer diagnosis. A similar immunodeficiency that impaired tumor surveillance was documented in mice with short telomeres. We conclude that STS patients' predisposition to solid cancers is due to T cell exhaustion rather than autonomous defects in the neoplastic cells themselves. [Display omitted] • Patients with short telomere syndromes (STS) have lower incidence of most solid cancers • Squamous cancers that arise lack hallmarks of chromosome instability • Cancers arise primarily due to short telomere-mediated T cell immunodeficiency • T cell exhaustion in STS mice fails to survey and suppress immunogenic tumors Schratz et al. find a surprisingly low incidence of solid cancers in patients with short telomere syndromes except for squamous tumors. Tumors show no genome instability and arise in patients with short telomere-induced T cell immunodeficiency. T cell exhaustion in short telomere mice fails to survey and suppress tumors. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes (PROs) (eg, symptoms, functioning) can inform patient management. However, patients and clinicians often have difficulty interpreting score meaning. The authors tested approaches for presenting PRO data to improve interpretability.Methods: This mixed-methods study included an Internet survey of cancer patients/survivors, oncology clinicians, and PRO researchers circulated via snowball sampling, plus individual in-person interviews. Clinical importance was conveyed using 3 approaches (presented in random order): normal score range shaded green, concerning scores circled in red, and red threshold lines indicating normal versus concerning scores. Versions also tested 2 approaches to score directionality: higher = more (better for function, worse for symptoms) and higher = better for both function and symptoms. Qualitative data from online comments and in-person interviews supplemented quantitative results on interpretation accuracy, clarity, and the "most useful" format.Results: The survey included 1113 respondents: 627 survivors, 236 clinicians, and 250 researchers, plus 10 patients and 10 clinicians who were purposively sampled interviewees. Interpretation accuracy ranged from 53% to 100%. The formats in which higher = better were interpreted more accurately versus those in which higher = more (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.07-1.58) and were more likely to be rated "very"/"somewhat" clear (OR, 1.39; 95% CI, 1.13-1.70) and "very" clear (OR, 1.36; 95% CI, 1.18-1.58). Red circle formats were interpreted more accurately than green-shaded formats when the first format presented (OR, 1.29; 95% CI, 1.00-1.65). Threshold-line formats were more likely to be rated "very" clear than green-shaded (OR, 1.43; 95% CI, 1.19-1.71) and red-circled (OR, 1.22, 95% CI, 1.02-1.46) formats. Threshold lines were most often selected as "most useful."Conclusions: The current results support presenting PRO data with higher = better directionality and threshold lines indicating normal versus concerning scores. Cancer 2017;123:1848-1859. © 2017 The Authors. Cancer published byWiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations aremade. [ABSTRACT FROM AUTHOR]

Objectives: Large numbers of elderly patients in the USA receive no treatment for esophageal cancer, despite evidence that multimodality treatment can increase survival. Our goal is to identify factors that may contribute to lack of treatment.Materials and Methods: Using Surveillance Epidemiology and End Results (SEER)-Medicare Linked Database (2001-2009), we identified regional esophageal cancer patients ≥65 years old. Treatment was defined as receiving any medical or surgical therapy for esophageal cancer. Logistic regression analysis was performed to identify factors associated with failure to receive treatment. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox proportional hazard model.Results: There were 5072 patients (median age, 75 years; interquartile range (IQR), 71-81 years). Majority were treated with definitive chemoradiation (48.49 %). Factors associated with lack of treatment included West geographic region and ≥80 years old. Patients who received therapy had better OS (log-rank, p < 0.001). Compared with treated patients, non-treated patients had worse adjusted OS (HR, 1.43; 95 % confidence interval (CI), 1.33-1.55; p < 0.001).Conclusions: Elderly patients with locally advanced esophageal cancer who received treatment had improved 5-year survival compared with patients without treatment. Disparities in utilization of treatment are associated with regional and socioeconomic factors, not presence of comorbidities. [ABSTRACT FROM AUTHOR]

Background: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation.Methods: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked.Results: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes.Conclusions: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .). [ABSTRACT FROM AUTHOR]

Purpose To estimate the association between cancer survivors' comorbid condition care quality and costs; to determine whether the association differs between cancer survivors and other patients. Methods Using the SEER-Medicare-linked database, we identified survivors of breast, prostate, and colorectal cancers who were diagnosed in 2004, enrolled in Medicare fee-for-service for at least 12 months before diagnosis, and survived $ 3 years. Quality of care was assessed using nine process indicators for chronic conditions, and a composite indicator representing seven avoidable outcomes. Total costs on the basis of Medicare amount paid were grouped as inpatient and outpatient. We examined the association between care quality and costs for cancer survivors, and compared this association among 2:1 frequency-matched noncancer controls, using comparisons of means and generalized linear regressions. Results Our sample included 8,661 cancer survivors and 17,332 matched noncancer controls. Receipt of recommended care was associated with higher outpatient costs for eight indicators, and higher inpatient and total costs for five indicators. For three measures (visit every 6 months for patients with chronic obstructive pulmonary disease or diabetes, and glycosylated hemoglobin or fructosamine every 6 months for patients with diabetes), costs for cancer survivors who received recommended care increased less than for noncancer controls. The absence of avoidable events was associated with lower costs of each type. An annual eye examination for patients with diabetes was associated with lower inpatient costs. Conclusion Higher-quality processes of care may not reduce short-term costs, but the prevention of avoidable outcomes reduces costs. The association between quality and cost was similar for cancer survivors and noncancer controls. [ABSTRACT FROM AUTHOR]

Purpose: Current standard of care conventional imaging modalities (CIM) such as X-ray computed tomography (CT) and bone scan can be limited for detection of metastatic prostate cancer and therefore improved imaging methods are an unmet clinical need. We evaluated the utility of a novel second-generation low molecular weight radiofluorinated prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer, [(18)F]DCFPyL, in patients with metastatic prostate cancer.Procedures: Nine patients with suspected prostate cancer recurrence, eight with CIM evidence of metastatic prostate cancer and one with biochemical recurrence, were imaged with [(18)F]DCFPyL PET/CT. Eight of the patients had contemporaneous CIM for comparison. A lesion-by-lesion comparison of the detection of suspected sites of metastatic prostate cancer was carried out between PET and CIM. Statistical analysis for estimated proportions of inter-modality agreement for detection of metastatic disease was calculated accounting for intra-patient correlation using general estimating equation (GEE) intercept-only regression models.Results: One hundred thirty-nine sites of PET positive [(18)F]DCFPyL uptake (138 definite, 1 equivocal) for metastatic disease were detected in the eight patients with available comparison CIM. By contrast, only 45 lesions were identified on CIM (30 definite, 15 equivocal). When lesions were negative or equivocal on CIM, it was estimated that a large portion of these lesions or 0.72 (95 % confidence interval (CI) 0.55-0.84) would be positive on [(18)F]DCFPyL PET. Conversely, of those lesions negative or equivocal on [(18)F]DCFPyL PET, it was estimated that only a very small proportion or 0.03 (95 % CI 0.01-0.07) would be positive on CIM. Delayed 2-h-post-injection time point PET yielded higher tumor radiotracer uptake and higher tumor-to-background ratios than an earlier 1-h-post-injection time point.Conclusions: A novel PSMA-targeted PET radiotracer, [(18)F]DCFPyL, was able to a large number of suspected sites of prostate cancer, many of which were occult or equivocal by CIM. This study provides strong preliminary evidence for the use of this second-generation PSMA-targeted PET radiotracer for detection of metastatic prostate cancer and lends further support for the importance of PSMA-targeted PET imaging in prostate cancer. [ABSTRACT FROM AUTHOR]

Outcomes of nonmyeloablative (NMA), HLA-haploidentical (haplo), related-donor allogeneic blood or marrow transplantation (allo-BMT) with high-dose post-transplantation cyclophosphamide (PTCy) appear to be similar to those using HLA-matched donors. Thus, it may be possible to prioritize donor factors other than HLA matching that could enhance antitumor activity. The Fc receptor polymorphism FCGR3A -158VV may confer greater sensitivity to rituximab than FCGR3A -158FF. In a prospective phase II study of NMA, related-donor allo-BMT with PTCy and post-transplantation rituximab for patients with B cell lymphomas, we hypothesized that donor selection that prioritized FCGR3A-158 polymorphism over HLA matching would be feasible, safe, and improve outcomes. The primary endpoint was 1-year progression-free survival (PFS). Of 83 patients transplanted (median age, 59 years), 69 (83%) received haplo grafts. Fifty-four (65%) received a graft that maintained or improved their Fc receptor polymorphism status. With 2.6-year median follow-up, the 1-year PFS and overall survival (OS) probabilities were 71% and 86%, respectively, with 1-year relapse and nonrelapse mortality (NRM) probabilities of 20% and 8%. At 1 year, the probability of acute grades II to IV graft-versus-host disease (GVHD) was 41%, with acute grades III to IV GVHD probability of 5% and chronic GVHD probability of 11%. Among haplo transplants, the 1-year probabilities of PFS, OS, relapse, and NRM were 70%, 83%, 20%, and 10%, respectively. No differences in outcomes were observed based on donor FCGR3A-158 polymorphism. Excess infection risk was not apparent with post-transplantation rituximab. Although donor selection based on FCGR3A-158 polymorphism was not shown to influence PFS, this study suggests that donor selection based on criteria other than best HLA match is feasible and safe. This study opens the way for the future investigation of donor prioritization based on promising non-HLA factors that may improve antitumor activity and decrease relapse after allo-BMT. This study was registered at www.clinicaltrials.gov as NCT00946023 . [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcome (PRO) measures are increasingly being used in clinical practice to inform individual patient management, but evidence is needed on which PROs are best suited for clinical use. Methods: This controlled trial randomly assigned patients with breast and prostate cancer undergoing treatment to complete one of three PRO measures: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (QLQ-C30), Supportive Care Needs Survey-Short Form (SCNS-SF34), or six domains from the Patient-Reported Outcomes Measurement Information System (PROMIS). Patients completed the PRO measures before clinic visits, and the results were provided to both the patient and clinician. At treatment completion, patients and clinicians completed brief feedback forms on the intervention's usefulness and value. Exit interviews were conducted with patients (at end of treatment) and clinicians (at end of study). The primary outcome was the proportion of patients in each arm who either strongly agreed or agreed to all feedback form items. Results: Of 294 eligible patients invited to participate, 224 (76%) enrolled (median age 66 years, 78% white, 72% prostate). Of the 181 patients (81%) who completed at least one feedback form item, participants in the QLQ-C30 study arm were most likely to strongly agree/agree to all items (74%) followed by PROMIS (61%) and SCNS-SF34 (52%; P=.03). Of the 116 participants (52%) who completed all feedback form items, the results were similar: 82% for the QLQ-C30, 62% for PROMIS, and 56% for SCNS-SF34 (P=.05). Clinicians did not prefer one questionnaire over the others. Conclusion: These results suggest that, when using PROs in clinical practice for patient management, the measure matters in terms of usefulness to patients. [ABSTRACT FROM AUTHOR]

• The clinical outcome for older adults with ALL or ABL ineligible for multi-agent chemotherapy are poor and are a rare, unmet need. • Entinostat plus clofarabine was well tolerated but infectious and metabolic derangements were more common in the older population (vs younger). • Events of hyperglycemia and peripheral neuropathy were not appreciated with the use of Entinostat plus clofarabine. • Entinostat plus clofarabine appears to be active in older adults with de novo ALL/ABL, and further study of this combination should be considered. Despite advances in immunotherapies, the prognosis for adults with Philadelphia chromosome-negative, newly diagnosed (ND) or relapsed/refractory (R/R) acute lymphoblastic leukemia/acute biphenotypic leukemia (ALL/ABL) remains poor. The benzamide derivative entinostat inhibits histone deacetylase and induces histone hyperacetylation. The purine nucleoside analogue clofarabine is FDA-approved for R/R ALL in children 1−21 years of age. Low doses of clofarabine have been reported to induce DNA hypomethylation. We conducted a phase 1 study of low dose clofarabine with escalating doses of entinostat in adults with ND or R/R ALL/ABL. Adults ≥60 years with ND ALL/ABL or ≥21 years with R/R ALL/ABL received repeated cycles every 3 weeks of entinostat (4 mg, 6 mg or 8 mg orally days 1 and 8) and clofarabine (10 mg/m2/day IV for 5 days, days 3–7) (Arm A). Adults aged 40–59 years with ND ALL/ABL or age ≥21 years in first relapse received entinostat and clofarabine prior to traditional chemotherapy on day 11 (Arm B). Changes in DNA damage, global protein lysine acetylation, myeloid-derived suppressor cells and monocytes were measured in PBMCs before and during therapy. Twenty-eight patients were treated at three entinostat dose levels with the maximum administered dose being entinostat 8 mg. The regimen was well tolerated with infectious and metabolic derangements more common in the older population versus the younger cohort. There was no severe hyperglycemia and no peripheral neuropathy in this small study. There were 2 deaths (1 sepsis, 1 intracranial bleed). Overall response rate was 32 %; it was 50 % for ND ALL/ABL. Entinostat increased global protein acetylation and inhibited immunosuppressive monocyte subpopulations, while clofarabine induced DNA damage in all cell subsets examined. Entinostat plus clofarabine appears to be tolerable and active in older adults with ND ALL/ABL, but less active in R/R patients. Further evaluation of this regimen in ND ALL/ABL appears warranted. [ABSTRACT FROM AUTHOR]

Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer. [Copyright &y& Elsevier]

BACKGROUND: Vascular endothelial growth factor is up-regulated in hepatocellular carcinoma (HCC) and is further up-regulated after transhepatic arterial chemoembolization. The authors of this report conducted a phase 2 trial to evaluate the safety and efficacy of bevacizumab combined with chemoembolization in patients with unresectable HCC. METHODS: Patients who had an Eastern Cooperative Oncology Group performance of status 0 to 2, a Child-Pugh score of A or B, and Barcelona Clinic Liver Cancer stage B or C HCC were eligible. Treatment consisted of bevacizumab every 2 weeks and chemoembolization during the third week of a 6-week cycle for up to 3 cycles over 6 months. The primary endpoints were safety and efficacy. RESULTS: Twenty-five patients received chemoembolization and bevacizumab. The most common grade 3 and 4 events after the first treatment cycle were leukocytopenia (12%), fatigue (12%), and hyponatremia (12%). Serious toxicities that had a known association with bevacizumab were observed in 4 patients. Thirty-day mortality was 0%. The median time to tumor progression for the targeted lesions was not reached, and overall survival was 10.8 months. The objective response rate was 60% using enhancement response evaluation criteria, and the disease control rate was 100%. CONCLUSIONS: Concurrent treatment with bevacizumab and chemoembolization was safe in carefully selected patients and demonstrated antitumor activity in patients with unresectable HCC. These results support the further development of bevacizumab combined with chemoembolization as a treatment for unresectable HCC. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Autologous blood or marrow transplantation (ABMT) for low-grade lymphomas can prolong event-free survival (EFS) but requires long-term follow-up. We report one of the longest follow-ups to a prospective transplantation study in such diseases. On a phase II study, 80 patients with low-grade, transformed, or mantle cell lymphoma received ABMT with 4-hydroperoxycyclophosphamide (4-HC) purging as part of initial or salvage therapy. Diagnoses included nontransformed follicular lymphoma in 63% and transformed lymphoma in 15%. With 16.6-year median follow-up for survival, actuarial 10-year EFS and overall survival (OS) were 34% (95% confidence interval [CI], 25%-46%) and 45% (35%-57%). Median EFS and OS were 3.0 and 8.0 years. Early nonrelapse mortality incidence was 8%; myelodysplastic syndrome or leukemia incidence was 4%. Most relapses occurred within 3 years, with a median time to diagnosis of relapse of 1.8 years (range: 0.1-15.6 years). On multivariate analysis, age >50 years, ≥3 prior chemotherapy regimens, and ABMT after relapse were associated with significantly inferior survival. Fifteen patients (19%) were event-free >15 years after transplantation, raising the possibility of a plateau in the progression-free survival curve. Thus, 4-HC-purged ABMT can produce extended remissions in a subgroup of patients with indolent lymphomas. [Copyright &y& Elsevier]

Purpose: Although patients' function, symptoms, and supportive care needs are obviously related, a better understanding of these relationships could improve patient management.Methods: In this cross-sectional, observational study, 117 cancer patients completed the Supportive Care Needs Survey-34 and EORTC-QLQ-C30. Each symptom and function domain from the EORTC-QLQ-C30 was dichotomized (high vs. low) using a cut-off of reference sample mean scores. Each need domain was dichotomized using a cut-off of an average score representing an unmet need. We explored within-patient patterns of function, symptom, and need domains using latent class analysis. Based on these patterns, patients were categorized as high versus low function; high versus low symptom; and high versus low need. We examined the concordance between categorizations of patients' function, symptoms, and needs.Results: The categorizations of function, symptoms, and needs were concordant for 66 patients (56%). Among patients with deficits in at least one area (n = 68), categorizations for 51 patients (75%) were discordant.Conclusions: About 50% of patients have similar classifications of their level of function, symptoms, and needs, but discordance was common among patients with deficits in at least one area, emphasizing the importance of assessing all of these outcomes as part of patient evaluations. [ABSTRACT FROM AUTHOR]