bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel deformation forecasting method utilizing comprehensive observation data
Authors: Du Sunwen , Li Yao
Published: September 2018

Mine disasters often happen unpredictably and it is necessary to find an effective deformation forecasting method. A model between deformation data and the factors data that affected deformation is built in this study. The factors contain hydro-geological factors and meteorological factors. Their relationship presents a complex nonlinear relationship which cannot be solved by ordinary methods such as multiple linear regression. With the development of artificial intelligence algorithm, Artificial Neural Network, Support Vector Machine, and Extreme Learning Machine come to the fore. Support Vector Machine could establish a deformation prediction model perfectly in the condition that there is less input data and output data. The deformation forecast model that uses quantum-behaved particle swarm optimization algorithm is selected to optimize the Support Vector Machine. The optimum configuration of Support Vector Machine model needs to be determined by two parameters, that is, normalized mean square error and correlation coefficient (R). Quantum-behaved particle swarm optimization could determine the optimal parameter values by minimizing normalized mean square error. It investigates the application effect of the proposed quantum-behaved particle swarm optimization–Support Vector Machine model by comparing their performances of popular forecasting models, such as Support Vector Machine, GA-Support Vector Machine, and particle swarm optimization–Support Vector Machine models. The results show that the proposed model has better performances in mine slope surface deformation and is superior to its rivals.
Item-specific and relational processing both improve recall accuracy in the DRM paradigm
Authors: Huff Mark J , Bodner Glen E
Published: September 2018

Using the Deese–Roediger–McDermott (DRM) paradigm, Huff and Bodner found that both item-specific and relational variants of a task improved correct recognition, but only the item-specific variants reduced false recognition, relative to a read-control condition. Here, we examined the outcome pattern when memory was tested using free recall, using the same item-specific versus relational task variants across three experiments as our previous study (processing instructions, pleasantness ratings, anagram generation). The outcome pattern in recall was similar to recognition, except relational processing at study actually reduced the DRM illusion, though not as much as item-specific processing. To reconcile this task difference, we suggest that the memory information laid down during relational encoding enhances the familiarity of the critical items at test. To the extent that familiarity is used less as a basis for responding in free recall than in recognition, relational processing ironically reduces rather than increases the DRM illusion in recall.
Medical Comorbidities and Functional Dependent Living Are Independent Risk Factors for Short-Term Complications Following Osteotomy Procedures about the Knee
Authors: Cotter Eric J. , Gowd Anirudh K. , Bohl Daniel D. , Getgood Alan , Cole Brian J. , Frank Rachel M.
Published: September 2018

Objective

To characterize rates and risk factors for adverse events following distal femoral osteotomy (DFO), high tibial osteotomy (HTO), and tibial tubercle osteotomy (TTO) procedures.

Design

Patients undergoing DFO, HTO, or TTO procedures during 2005 to 2016 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Rates of adverse events were characterized for each procedure. Demographic, comorbidity, and procedural factors were tested for association with occurrence of any adverse events.

Results

A total of 1,083 patients were identified. Of these, 305 (28%) underwent DFO, 273 (25%) underwent HTO, and 505 (47%) underwent TTO. Mean ages for patients undergoing each procedure were the following: DFO, 51 ± 23 years; HTO, 40 ± 13 years; and TTO, 31 ± 11 years. The most common comorbidities for DFO were hypertension (34%) and smoking (17%); for HTO, hypertension (22%) and smoking (21%); and for TTO, smoking (20%) and hypertension (11%). Independent risk factors for occurrence of any adverse event were age ⩾45 years for DFO (odds ratio [OR] = 3.1, P < 0.001) and HTO (OR = 2.3, P = 0.029), and body mass index >30 for HTO (OR = 2.5, 95% confidence interval = 1.1-5.7, P = 0.031). When all osteotomy procedures were analyzed collectively, additional variables including diabetes mellitus (OR = 2.2, P = 0.017), chronic obstructive pulmonary disease (OR = 5.5, P = 0.003), and dependent functional status (OR = 3.0, P = 0.004) were associated with adverse events.

Conclusions

The total rate of adverse events was not independently associated with the type of osteotomy procedure. In addition, patients with age >45, diabetes mellitus, chronic obstructive pulmonary disease, and dependent functional status have greater odds for adverse events and should be counseled and monitored accordingly.
Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature
Authors: Volmer Timm , Effenberger Timo , Trautner Christoph , Buhl Roland
Published: September 2018

This review provides an overview of the role of long-term treatment of severe asthma with oral corticosteroids (OCS) and its associated side-effects in adults. It is based on a systematic literature search conducted in MEDLINE, Embase and the Cochrane Library to identify relevant studies. After a short overview of severe asthma and its treatment we present studies showing a dose–response relationship in asthmatic patients treated with OCS and then consider by organ systems the undesired effects demonstrated in clinical and epidemiological studies in patients with OCS-dependent asthma. It was found that the risk of developing various OCS-related complications, including infections, diabetes and osteoporosis as well as psychiatric disorders, was higher for patients with long-term exposure to OCS compared with control groups. In addition, studies showed a significant increase in healthcare resource utilisation due to OCS treatment. Therefore, it is incumbent on every clinician to carefully weigh the potential beneﬁt of preventing loss of asthma control against this risk before opting to prescribe long-term OCS therapy. Effective corticosteroid-sparing strategies must be used and should aim at short-term use with the lowest effective dose and start tapering as soon as possible until OCS therapy is terminated.
Comparing retrospective and panel data collection methods to assess labor market dynamics
Authors: Assaad Ragui , Krafft Caroline , Yassin Shaimaa
Published: September 2018

There is potential for measurement problems in both retrospective and panel microdata. In this paper, we compare results on basic indicators related to labor markets and their dynamics from retrospective and panel survey data in Egypt, in order to determine the conditions under which results are similar or different. Specifically, we (1) assess the consistency of reporting of time-invariant characteristics in different waves of the panel, (2) compare the retrospective and panel data results on past labor market statuses, (3) assess the consistency of estimates of labor market transition rates across two specific dates by comparing panel and retrospective data, (4) assess the consistency of estimates of the level and trends of annual labor market transition rates across retrospective data from different waves of the survey, and (5) assess whether retrospective data can provide accurate trends of labor market aggregates, such as unemployment rates. We find that it is possible to garner useful information on labor market dynamics from retrospective data, but one must be cautious about which information to trust and at what level of detail. We conclude with a discussion of implications for future research as well as future survey design.

JEL Classification:C83, C81, J01, J62, J64
The effect of immigration shocks on native fertility outcomes: evidence from a natural experiment
Authors: Seah Kelvin K. C.
Published: September 2018

ᅟ

This paper investigates whether immigration shocks have a causal effect on native fertility patterns. It uses a natural experiment, exploiting the large, unexpected and localised immigration of Cuban nationals to the Miami area in the USA in 1980 to examine the fertility consequences for non-Cuban Miami women. Using a synthetic control estimator and an extended individual difference-in-differences analysis, the results from this study indicate that the immigration shock had an overall negative, though short-lived, impact on the fertility of Miami women. In addition, fertility effects are found to vary by homeownership: While the immigration shock had a considerable negative impact on the fertility of women living in rented homes, it had no effect on those living in owned homes. This differential impact was likely due to the rise in local housing rents accompanying immigration, making childbearing less affordable for those living in rented homes.

JEL Classification: J61, J13
American Cancer Society (ACS) Nutrition and Physical Activity Guidelines after colon cancer diagnosis and disease-free (DFS), recurrence-free (RFS), and overall survival (OS) in CALGB 89803 (Alliance).
Authors: Van Blarigan Erin , Fuchs Charles S. , Niedzwiecki Donna , Ye Xing , Zhang Sui , Song Mingyang , Saltz Leonard , Mayer Robert J. , Mowat Rex B. , Whittom Renaud , Hantel Alexander , Benson Al Bowen , Atienza Daniel M. , Messino Michael J. , Kindler Hedy L. , Venook Alan P. , Ogino Shuji , Willett Walter C. , Giovannucci Edward L. , Meyerhardt Jeffrey A.
Published: September 2018

10006

Background: The ACS Nutrition and Physical Activity Guidelines for Cancer Survivors include: 1) healthy body weight; 2) physical activity; and 3) a diet high in vegetables, fruits, and whole grains. It is not known whether colon cancer patients who follow these guidelines have improved DFS, RFS, or OS. Methods: We conducted a prospective study among 992 stage III colon cancer patients enrolled in an adjuvant chemotherapy trial in 1999-2001. Lifestyle was assessed twice. We applied a score developed by McCullough ML et al. to quantify adherence to the ACS guidelines based on BMI; physical activity; and intake of vegetables, fruits, whole grains, and red/processed meats (range: 0-6; higher = more healthy behaviors). Alcohol is included in the ACS guidelines for cancer prevention, but not cancer survivors; we tested the score without and with alcohol using McCullough et al.’s cut points: 0 pts = >1/d for women, >2/d for men; 1 pt = no alcohol; 2 pts = >0-1/d for women, >0-2/d for men. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for DFS, RFS, and OS adjusting for clinical, demographic, and lifestyle factors. Results: Over 7 y median follow-up, we observed 335 recurrences and 299 deaths (43 without recurrence). Compared to patients with 0-1 pt (262, 26%), patients with 5-6 pts (91, 9%) had 42% lower risk of death (HR: 0.58; 95% CI: 0.34, 0.99; p-trend: 0.01) and a trend toward improved DFS (HR: 0.69; 95% CI: 0.45, 1.06; p-trend: 0.03). When including alcohol in the score, the adjusted HR’s comparing patients with 6-8 pts (162; 16%) to 0-2 pts (187; 91%) were: 0.49 for OS (95% CI: 0.32, 0.76; p-trend: 0.002), 0.58 for DFS (95% CI: 0.40, 0.84; p-trend: 0.01), and 0.64 for RFS (95% CI: 0.44, 0.94; p-trend: 0.05). Conclusions: Colon cancer patients with a healthy body weight who engaged in physical activity, ate a diet high in whole grains, vegetables, and fruits and low in red/processed meats, and drank moderate alcohol had longer DFS and OS than patients who did not engage in these behaviors. Support: U10CA180821, U10CA180882, U10CA180820, K07CA197077, R01CA118553, P50CA127003, R35CA197735. ClinicalTrials.gov:NCT00003835.
Receipt of recommended surveillance with imaging in survivors of early stage non-small cell lung cancer.
Authors: Malhotra Jyoti , Rotter David , Jabbour Salma , Aisner Joseph , Lin Yong , Manne Sharon , Demissie Kitaw
Published: September 2018

10017

Background: Lung cancer survivors have a high risk for recurrence and second cancers and a 5-year survival of only 50%. Imaging surveillance for early cancer detection in this group is recommended for life. We measured the rates and determinants of regular surveillance imaging in non-small cell lung cancer (NSCLC) survivors. Methods: Using the Surveillance Epidemiology and End Results (SEER)-Medicare linked database, we identified 10680 patients with stage I and II NSCLC, age ≥ 66 years diagnosed from 2001-2011 and treated with surgery. Patients were censored at the time of recurrence/second cancer, loss of insurance or 3 months before death. Receipt of a CT and/or PET scan during the surveillance periods of 7 to 18, 19 to 30, 31 to 42 and 43 to 60 months from the date of surgery was assessed. Percentage of patients’ receiving regular imaging up to 18, 30 and 60 months of follow-up was determined. Adjusted cox regression was used to measure the effect of receiving recommended imaging on survival. Results: Overall, 79% and 40% survivors had follow-up information till the end of 30-month and 60-month surveillance periods respectively. Forty nine percent survivors were male and 86% were white. With a median follow-up of 7.6 years, 71% of the survivors received imaging in the first 18 months after surgery, but only 56% and 44% of survivors continued to receive regular imaging by 30-month and 60-month of follow-up periods respectively. Survivors were less likely to receive imaging if they were older (≥80 years), black, not married, had rural residence, did not receive adjuvant therapy, had stage I disease (compared to stage II) and were diagnosed in 2006 or earlier. In adjusted analysis, survivors receiving recommended imaging up to 18 months from surgery had improved survival compared to survivors who did not (HR 0.86; 95% CI 0.81-0.92). Survival benefit was also observed in survivors who had regular imaging up to 5 years from surgery (HR 0.68; 95% CI 0.60-0.76). Conclusions: More than half the lung cancer survivors did not receive recommended long-term surveillance imaging especially if older, black or with rural residence. Adherence to regular surveillance even at 5 years from initial surgery is associated with improved survival.
Mitochondrial DNA content in peripheral blood as a biomarker for cancer-related fatigue in early-stage breast cancer patients: A prospective cohort study.
Authors: Chae Jung-Woo , Chua Peh Siang , NG Terence , Yeo Hui Ling Angie , Shwe Maung , Gan Yan Xiang , Dorajoo Sreemanee Raaj , Foo Koon Mian , Loh Kiley Wei Jen , Koo Si-Lin , Chay Wen Yee , Tan Tira Jing Ying , Beh Sok Yuen , Lim Hsuen Elaine , Lee Guek Eng , Dent Rebecca Alexandra , Yap Yoon Sim , Ng Raymond C.H. , Ho Han Kiat , Chan Alexandre
Published: September 2018

10018

Background: Cancer-related fatigue (CRF) is reported to be associated with mitochondrial dysfunction. Hence, mitochondrial DNA (mtDNA) content, a biomarker of mitochondrial dysfunction, is hypothesized to correlate with the onset of CRF. This study aimed to evaluate the association between peripheral blood mtDNA content and CRF in patients receiving chemotherapy. Methods: This was a prospective cohort study. Early-stage breast cancer patients (Stages I to III) receiving anthracycline or taxane-based chemotherapy were recruited. CRF was assessed using the validated Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at two time points: baseline (T1; prior to treatment) and 6 weeks after initiation of treatment (T2). Worsening of CRF was defined as ≥10% increase in the overall MFSI-SF score at T2. Peripheral blood mtDNA content was measured at both time points using real-time quantitative polymerase chain reaction. Multiple logistic regression was utilized to evaluate the association between mtDNA reduction and worsening of CRF, adjusting for age, anxiety, insomnia and other clinically important covariates. Results: A total of 91 patients [mean age (±SD): 51.3 (9.2) years; 81.3% Chinese; 63.3% receiving anthracycline-based chemotherapy] were recruited. Proportions of patients with worsening of CRF increased from the lower to the upper quartiles of mtDNA reduction (26.1%, 30.4%, 52.2%, and 59.1% in quartiles 1, 2, 3, and 4, respectively, P = 0.010 for trend). Reduction of mtDNA content was significantly greater among those with worsening of CRF compared to those without CRF [mean reduction (±SD): 16.3 (23.5) vs 6.0 (17.3), P = 0.018]. After adjusting for covariates, every 1-unit reduction of the mtDNA content was associated with a 4% increase risk for worsening of CRF (95% CI, 1%-8%; P = 0.016). Conclusions: This is the first study to show that reduction of mtDNA content in peripheral blood is associated with onset of CRF in patients receiving chemotherapy. Further validation studies are required to confirm the findings.
Agreement about end-of-life (EOL) care among advanced cancer patients and their caregivers: Associations with care received.
Authors: Kamen Charles Stewart , Duberstein Paul , Prigerson Holly Gwen , Mohile Supriya Gupta , Asare Matthew , Janelsins Michelle Christine , Mustian Karen Michelle , Peppone Luke Joseph , Epstein Ronald M.
Published: September 2018

10021

Background: Patients with advanced cancer and their caregivers often have different preferences regarding patients’ EOL care. Disagreement in a patient-caregiver dyad can increase stress and result in suboptimal care. Understanding factors that promote agreement, as well as the effect of agreement on care received at EOL, can inform interventions to improve communication and EOL decision-making for patients and caregivers. Methods: 205 patients (Stage III or IV cancer plus limited prognosis) and their caregivers were recruited to a randomized controlled trial of a communication intervention for patients, caregivers, and providers (Cancer Communication Study, PI: Epstein). Before intervention, patients completed the Preferences for Life-Extending Treatment questionnaire, which asked their preference regarding experimental treatment, life support, and palliative care; caregivers were asked about patients’ preferences. Binomial logistic regressions analyses modeled agreement in preferences as a function of patient and caregiver demographic characteristics and EOL care received as a function of patient-caregiver agreement. Results: The majority of patient-caregiver dyads agreed about experimental treatment (60.3%), life support (63.4%), and palliative care (70.7%). Dyads were more likely to agree about palliative care when patients were female (OR = 1.94, p = .03) and non-Hispanic white (OR = 2.10, p = .07) and when caregivers were college educated (OR = 2.04, p = .03). Of the 82 patients who died during study follow-up, 57 (69.5%) received EOL care congruent with their preferences. In 19 of the 38 (50%) cases where patient-caregiver dyads disagreed, caregivers’ preferences predicted EOL care received. Dyadic agreement about life support was associated with increased odds of patients receiving/not receiving life support congruent with their preference (OR = 3.02, p = .02). Conclusions: Facilitating agreement between patients and caregivers could improve receipt of patient-centered care. A communication intervention designed to increase dyadic agreement by helping patients and caregivers discuss challenging EOL decisions might improve EOL care delivery. Clinical trial information: NCT01485627.
Latino ethnicity, immigrant status, and preference for life-extending end-of-life cancer care.
Authors: Tergas Ana Isabel , Prigerson Holly Gwen , Shen Megan Johnson , Maciejewski Paul K
Published: September 2018

10028

Background: Latino advanced cancer patients are less likely to engage in advance care planning, use hospice services, and receive end-of-life (EOL) care in line with their preferences compared to non-Latino advanced cancer patients. Little is known about how immigration status influences preference for life-extending care (LEC) at the EOL. Methods: Data were derived from two sequential multi-institutional, longitudinal cohort studies of patients with advanced cancer recruited from 2002 – 2008 (Coping with Cancer I [CwC-1]) and 2010 – 2015 (Coping with Cancer II [CwC-2]). Multiple logistic regression analysis was used to estimate effects of immigrant status and CwC cohort among Latinos, and effects of ethnicity and CwC cohort among US-born Latinos and non-Latino whites, on preference for LEC at the EOL. Results: Of the 760 studied cancer patients, 661 were US-born non-Latino (US non-L), 34 were US-born Latino (USL) and 65 were Latino immigrants (LI). LI were less educated (mean years of education: 7.8 years) than USL (11.1 years), who were in turn less educated than US non-L (13.7 years). Far fewer LI had insurance compared to USL (18.5% vs. 64.7%, respectively; p < 0.001), and fewer USL had insurance compared to US non-L (64.7% vs. 81.4%, respectively; p = 0.017). Within CwC-2, LI had higher odds of preferring LEC over comfort care compared to USL (adjusted odds ratio [AOR] = 9.4; 95% CI: 1.2, 72.4), and USL had lower odds of preferring LEC compared to US non-L (AOR = 0.3; 95% CI: 0.1, 1.0). LI from CwC-2 had higher odds of preferring LEC compared to LI from CwC-1 (AOR = 11.4; 95% CI: 2.7, 48.4), but there was no difference between USL from CwC-2 and USL from CwC-1. US non-L from CwC-2 had higher odds of preferring LEC compared to US non-L from CwC-1 (AOR = 3.9; 95% CI: 2.6, 5.9). Within CwC-1, there was no difference in LEC preference between LI and USL, nor between USL and US non-L. Conclusions: Immigrant status has a strong effect on preference for life-extending care among the more recent cohort of Latino cancer patients. Preference for life-extending care appears to have increased significantly over time for Latino immigrants, but remained unchanged for US-born Latinos. Latino immigrants may increasingly want life-extending care near death.
Accrual of older adults to Canadian Cancer Trials Group (CCTG) led trials: A retrospective analysis from 1990 to 2015.
Authors: Hernandez Torres Catalina , Cheung Winson Y. , O'Callaghan Christopher J. , Hsu Tina
Published: September 2018

10031

Background: Older adults (OA) age 65+ make up to 60% of all newly diagnosed cancers. However, only 22-32% of patients accrued in cooperative group studies in the 1990s were age 65+. In 2003, several studies suggested that clinical trial design, in particular the presence of strict exclusion criteria, was a major barrier to accrual of OA. The objective of this study was to determine: 1) whether there has been an improvement in accrual of OA to clinical trials led by the Canadian Cancer Trials Group (CCTG) over time; 2) clinical trial features associated with accrual of OA to clinical trials 3) whether exclusion criteria in trials initiated 2003 or after have been relaxed. Methods: All completed randomized Phase II and III CCTG-led clinical trials initiated between 1990 or later were included. Trial characteristics including tumor type, stage, treatment type, and exclusion/inclusion criteria, as well as percentage of OA age 65+ accrued were recorded. Association between percentage of OA accrued and trial characteristics were compared using the Wilcoxin rank sum test. Assessment of exclusion criteria before and after 2003 was compared using the Chi Square test or Fisher exact test. Results: A total of 68 trials were included. Most trials were phase III (73%), chemotherapy trials (48%), opened before 2003 (70.6%), advanced disease (73%) and lung cancer was the most common tumour site (17.6%). OA accrual remains low compared to OA diagnosed with cancer in Canada (41% vs. 56%, p < 0.001). There was an improvement in accrual of OA after 2003 (47.1% vs. 34.9%, p = 0.02). Tumour site, early stage disease, more restrictive performance status, requiring a new biopsy, and having a longer consent form, were associated with lower accrual of OA (p < 0.05). There was no significant loosening of exclusion with time though patients with pulmonary comorbidities were more likely to be excluded in studies initiated in 2003 or later (p = 0.006). Conclusions: OA remain under-represented in clinical trials. There has been no relaxing of exclusion criteria; however, exclusion based on comorbidities was not significantly associated with under accrual of OA in our study.
Patient-reported comorbidity and survival in older adults with cancer.
Authors: Williams Grant Richard , Deal Allison Mary , Lund Jennifer Leigh , Chang YunKyung , Muss Hyman B. , Pergolotti Mackenzi , Guerard Emily Jean , Shachar Shlomit S. , Sanoff Hanna Kelly
Published: September 2018

10033

Background: Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient as most clinical trials lack systematic measurement of comorbidities. The primary purpose of this study was to evaluate the prevalence and impact of patient-reported comorbidity on survival using various comorbidity scoring algorithms. Methods: We utilized a unique linkage of the Carolina Senior Registry, an institutional registry (NCT01137825) that contains geriatric assessment data, with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using a patient-reported version of the Older Americans Resources and Services Questionnaire (OARS) Physical Health subscale that includes information regarding 13 specific comorbid conditions and the degree to which each impairs function (“not at all” to “a great deal”). Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all-cause mortality. Results: 539 patients were successfully linked to mortality data. Median age 72, 72% female, 85% Caucasian, 47% breast cancer, and 12% lung cancer. 92% of participants reported at least one comorbid condition, mean of 2.7 conditions (range 0-10), with arthritis and hypertension the most common (52 and 50%, respectively). 62% of patients with a comorbid illness reported a functional limitation related to comorbidity. Both the presence of 3 or more total comorbidities (hazard ratio (HR) 1.44, CI 1.08-1.92) and 2 or more comorbidities impacting function (HR 1.46, CI 1.09-1.95) increased mortality. After adjusting for age, cancer type, and stage, the risk of death increased 12% for each comorbid condition impacting function (HR 1.12, CI 1.02-1.24), but did not significantly increase for the number of comorbid conditions alone (HR 1.07, CI 0.99-1.15). Conclusions: Comorbid conditions in older adults with cancer are highly prevalent, frequently impair function, and impact survival. Comorbid conditions that impair function have a greater impact on survival than the presence of comorbidity alone. Comorbidity assessment should be incorporated in clinical trials and can be measured via a simple one-page patient-reported questionnaire.
Immuno-oncology and the elderly: A comparative analysis of participation and toxicities of senior adults aged 65 years and above vs mid age and adolescent/young adult patients on immunotherapy-based phase I clinical trials.
Authors: Subbiah Ishwaria Mohan , Hess Kenneth R. , Fujii Takeo , Alshawa Anas , Lui Anna , Roy Sarath , Khanji Rahil , Subbiah Vivek , Naing Aung , Hong David S.
Published: September 2018

10034

Background: Senior adults ≥ 65 yrs remain underrepresented in early phase clinical trials in particular trials with novel immunotherapies. One general limitation to enrollment is the concern for immune-related toxicities in the context of older age and comorbidities. We analyzed the enrollment and incidence of toxicities of seniors in comparison to mid age and adolescent/young adult (AYA) pts enrolled in phase 1 immunotherapy trials. Methods: We identified 422 consecutive pts w advanced cancer treated on immunotherapy-based phase I trials bw 04/2009-09/2015. We divided pts into 3 cohorts based on age at start of trial (AYA 15-39y, mid age 40-64y, seniors 65y+) and collected pt/disease characteristics and immune-related adverse events (irAE) including endocrinopathies, diarrhea/colitis, pneumonitis, constitutional (eg fatigue, fever, anorexia), myalgia, and dermatitis. Results: Of 422 patients treated, 116 were seniors (27%, median 70y), 50 AYA (12%, median 30y), 256 mid age (61%, median 56y). Most common cancers were GI (n = 108, 26%), thoracic/head/neck (n = 84, 20%), GU (n = 54, 13%), and GYN (n = 47, 11%). Median PFS was comparable in all 3 cohorts (2.4m seniors, 2.1m AYA, 2.1m mid age). The incidence of irAE was higher in elderly than mid age or AYA (low grade [G1/2] 49% vs 34% vs 34%, p 0.02; high grade [G3/4] 19% vs 11% vs 12%. p 0.14). When comparing irAE rates of seniors to AYA and mid age pts, the odds ratio of high grade events was 1.81 (95% CI 1.01, 3.24; p 0.05) and low grade events was 1.85 (95% CI 1.20, 2.85; p 0.0055). Most common G1/2 irAE among all cohorts was fatigue (n = 76, 18%), dermatitis (n = 59, 14%), fever (n = 29, 7%) and anorexia (n = 28, 7%) with seniors having a greater incidence of low grade fatigue (25% vs 15%, OR 1.84, 95% CI 1.09, 3.10, p 0.025). Conclusions: Senior adults accounted for < 1/3 of pts on immunotherapy-based phase I trials. When compared to mid age and AYA pts, seniors had a higher likelihood of experiencing a toxicity. Early phase immunotherapy trials may be an option for older adults but with a particular vigilance for adverse events in this population.
The emotional toll of caregiving for older patients with advanced cancer: Baseline data from a multicenter geriatric assessment (GA) intervention study in the University of Rochester NCI Community Oncology Research Program (UR NCORP).
Authors: Mohile Supriya Gupta , Xu Huiwen , Canin Beverly E. , Plumb Sandy , Wells Megan , Flannery Marie Anne , Hoerger Michael , Kamen Charles Stewart , Hurria Arti , Dale William , Heckler Charles E. , Culakova Eva , Bautista Javier , Hopkins Judith O. , Liu Jijun , Peri Srihari , Geer Jodi , Mustian Karen Michelle , Morrow Gary R. , Duberstein Paul
Published: September 2018

10042

Background: Depression is common in caregivers (cgs) of patients (pts) with cancer. However, little is known about the association of health status of older pts with cancer with cg emotional health. Methods: Baseline data from a GA intervention study conducted at 68 oncology practices in the UR NCORP were analyzed. Pts aged ≥ 70 with an advanced solid tumor cancer or lymphoma with ≥ 1 GA impairment were enrolled; pts could enroll with 1 cg. Relationships between pt GA impairments (using 12 validated measures) and cg (spouses or live-in partners) emotional health including anxiety ( ≥ 5 on Generalized Anxiety Disorder-7 (GAD-7)), depression ( ≥ 2 on Patient Health Questionnaire-2), and distress ( ≥ 4 on distress thermometer) were evaluated in separate multivariate logistic models adjusted for pt (cancer type, treatment status) and cg (age, sex, race, education, income, comorbidity) characteristics. Results: Among 213 pts (mean age 76, 70-89), >50% had ≥ 5 impaired GA measures. Of the 213 cg (mean age 73, 52-91), 23% screened positive for anxiety, 16% for depression, and 40% for distress. In bivariate analyses, number of GA impairments, ≥ 1 fall, pt anxiety ( ≥ 5 on GAD-7) and depression ( ≥ 5 on Geriatric Depression Scale (GDS)) were associated with all 3 cg outcomes; pt activities of daily living (ADL) deficits were associated with cg depression and distress. In multivariate analysis, number of GA impairments was associated with cg distress. In separate models, pt ADL deficit and depression were associated with cg distress, and pt ADL deficit was associated with cg depression. GA variables were not associated with cg anxiety in multivariate analysis. Conclusions: A high proportion of cg of older pts with cancer report distress. GA can help identify cg at risk for poor emotional health. Interventions for cgs should address the health status of older pts with cancer. [Table: see text]
Evaluation of adolescents and young adults (AYA) attitudes towards participation in cancer clinical trials.
Authors: Gupta Abha A. , Bell Jennifer A.H , Wang Kate , Forcina Victoria , Tam Seline , Lin Yu-Chung , Taback Nathan , Mitchell Laura , Lewin Jeremy Howard
Published: September 2018

10047

Background: Participation in clinical trials (CT) for AYA ( < 39 years) remain the lowest of any patient group with cancer. Little is known about the personal barriers to AYA accrual. The aim of this study was to explore AYA attitudes that influence CT participation. Methods: A mixed methods approach included 1) qualitative: interpretive descriptive methodology guided individual semi-structured interviews with 21 AYA for factors influencing CT enrollment and 2) quantitative: AYA and non-AYA (≥40) matched for histology completed Cancer Treatment subscale of Attitudes toward Cancer Trials Scales (ACTS-CT) (Schuber, 2008) and 9 supplementary questions formed from interview analysis. Differences between AYA and non-AYA cohorts were analyzed using the Mann-Whitney U test and ordered logistic regression models were constructed for prediction of the effect of baseline demographics. Results: The major themes influencing CT participation were: (1) family/peer group opinion (2) CT impact on daily/future life (e.g. school; starting a family) and (3) illness severity/psychological readiness for CT information. Surveys were distributed to 61 AYA (median age: 29 years (17-39)); 74 non-AYA (55 (40-88)). Compared with non-AYA, AYA perceived CT to be unsafe/more difficult (Personal Barrier/Safety domain; p = 0.01). AYA were also more concerned with CT interference in their long term goals (p = 0.04). Logistic regression identified participants who had previously been offered a CT (p = 0.01) or who spoke English as their first language (80% of cohort)(p = 0.01) reported less barriers to CT. There were no differences based on age in other domains (Personal Benefits; Personal/Social Value; Trust in CT). In all participants, differences were seen in the Personal Benefits domain if respondents had children (p = 0.05) or were currently working (p = 0.04). Conclusions: Age-related differences in attitudes towards CT suggest that tailored approaches to CT accrual of different patient groups may be warranted. Patient-centered delivery of information regarding CT, particularly for those in whom English is a second language and who are trial-naïve, may improve accrual and warrants further prospective, randomized study.
TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM).
Authors: Freedman Rachel A. , Gelman Rebecca Sue , Melisko Michelle E. , Anders Carey K. , Moy Beverly , Blackwell Kimberly L. , Connolly Roisin M. , Niravath Polly Ann , Van Poznak Catherine H. , Puhalla Shannon , Farooq Sarah , Cropp Anne , Cotter Christine M , Liu Minetta C. , Krop Ian E. , Nangia Julie R. , Tung Nadine M. , Wolff Antonio C. , Winer Eric P. , Lin Nancy U.
Published: September 2018

1005

Background: Evidence-based treatments (tx) for metastatic, HER2+ BCBM are limited. We previously found a central nervous system (CNS) objective response rate (ORR) of 8% (95% CI 2-22%) for the irreversible, EGFR/HER2-targeted kinase inhibitor, neratinib. To enhance CNS activity, we evaluated the combination of neratinib + capecitabine in a subsequent cohort, and report results here. Methods: Pts with measurable BCBM (≥ 1 cm in longest dimension) and no prior lapatinib or capecitabine were eligible. All but 3 had CNS progression after local CNS tx. During 21 day cycles, pts received capecitabine 750 mg/m2 twice daily x 14 days followed by 7 days off + neratinib 240 mg orally once daily. Loperamide prophylaxis (16 mg total daily) was recommended during cycle 1. Brain MRI and non-CNS imaging were repeated every 2 cycles until 18 wks, then every 3 cycles. The primary endpoint was composite CNS ORR, requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions (central review, VORR), no progression of non-target or non-CNS lesions, no new lesions, no escalating steroids, and no progressive neurologic signs/symptoms. We used a two-stage design with hypotheses ORR 15% and 35% (error rates 5% and 20%), responses in ≥5/19 pts to enter 2ndstage; responses in ≥9/35 [26%] pts to be promising. Results: 39 pts enrolled between 4/2014-11/2016 (2 withdrew before tx, 37 analyzed); median age 51, median prior metastatic lines 2 (range 0-6), 65% had prior WBRT. As of 11/15/16, 23 (62%) patients are alive and 7 remain on protocol tx; median number of cycles initiated = 5 (range 1-26). 18 women (49%) had a VORR (95% CI 32-66%, neurologic exams not yet available on all pts). Overall 12-month survival is 63% (95% CI 43%-77%); 4/7 pts still on protocol therapy have not yet reached 6 cycles. No pts had grade 4 toxicity; 18 (49%) had grade 3 toxicity, with diarrhea most common (32%), and 6 pts discontinued tx for toxicity. Conclusions: The combination of neratinib and capecitabine is active for BCBM with VORR in nearly half of pts, supporting further development of the regimen for BCBM. Updated results will be presented at the meeting. Clinical trial information: NCT01494662.
What do social media-savvy cancer survivors tell us about the completeness of survivorship care plans?
Authors: Radford Diane Mary , Staley Alicia C. , Landercasper Jeffrey , Dietrich Leah L. , Vang Choua A , Borgert Andrew , Attai Deanna J.
Published: September 2018

10063

Background: The Commission on Cancer (CoC) standard 3.3 became effective in 1/2015 requiring the delivery of a survivorship care plan (SCP) at the completion of curative treatment. Both the CoC and ASCO have recommended minimum requirements for SCPs, which should include both a treatment summary and follow up care plan. Many cancer patients use social media (SM) as a way to obtain support and information. We have shown previously that the majority of SM savvy cancer survivors (88.2%) do not receive SCPs ( J Clin Oncol 35, 2017 suppl 5S; abstr 104). We sought to determine the contents of the SCPs received. Methods: An IRB-approved survey was conducted via the online tool SurveyMonkey from 3/21/2016 to 4/2/2016. Patients were invited to participate via SM outlets reaching cancer-related communities including Twitter chats, Facebook groups, blogs, and targeted emails. Results: A total of 312 patients responded. 63% (194) had completed curative treatment (excluding endocrine therapy). Of these 11.8% (23) reported receiving an SCP at the end of treatment. Of 22 patients who responded, 9/22 (40.9%) found the SCP helpful, 11/22 (50.0%) somewhat helpful, and 2/22 (9.1%) not helpful. The table below shows the components of those SCPs received. Conclusions: Not only did a small percentage of patients receive SCPs but also no patient received a complete SCP per the CoC and ASCO recommendations. Particularly deficient was a description of late/long-term effects of treatment—only 36% received such information. Challenges exist in the delivery of complete SCPs. [Table: see text]
Endocrine and metabolic diseases among colorectal cancer survivors in a population-based cohort.
Authors: Hawkins Makenzie , Soisson Sean Patrick , Blackburn Brenna , Rowe Kerry G. , Deshmukh Vikrant , Newman Michael , Wan Yuan , Fraser Alison M , Smith Ken R , Ulrich Cornelia M , Ganz Patricia A. , Samadder Niloy Jewel , Hashibe Mia
Published: September 2018

10074

Background: Colorectal cancer is the third most common cancer among men and women in the United States. As of 2016, there were an estimated 1.4 million colorectal cancer survivors. Research on endocrine and metabolic diseases over the long term in colorectal cancer survivors is limited. Obesity is a risk factor for colorectal cancer, thus it is of interest to investigate diseases that may share this risk factor such as diabetes for long term health effects among survivors. Methods: A total of 7,077 colorectal cancer patients who were diagnosed between 1997 to 2012 were identified in the Utah Population Database. A general population cohort of 35,354 individuals was matched on birth year, sex, birth state and follow-up time as a comparison group. Late effects were identified using electronic medical records and statewide ambulatory and inpatient data and were assessed over three time periods of 1-5 years, 5-10 years, and > 10 years. Cox proportional hazard models were used to estimate the risk of late effects after adjusting for matching factors, race, baseline body mass index, and the baseline Charlson Comorbidity Index. Results: Across all three time periods, late effects risk for endocrine diseases and metabolic disorders was significantly greater for colorectal cancer survivors compared to the general population cohort. Risk for diabetes mellitus with complications was significantly increased for survivors and risk was greatest for uncontrolled diabetes (HR = 5.04, 99%CI = 2.38, 10.67) and diabetes with neurological manifestations (HR = 4.10, 99%CI = 2.08, 8.26). Higher risk was also observed for thyroid disorders (HR = 3.09, 99%CI = 2.34, 4.08) and nutritional deficiencies (HR = 4.98, 99%CI = 3.47, 7.17). The risk of obesity in survivors was greatest 1-5 years post cancer diagnosis (HR = 5.04, 99%CI = 2.91, 8.75), but remained significantly increased at all follow-up time periods. Conclusions: Endocrine and metabolic diseases were significantly higher in colorectal cancer survivors across the follow-up periods. As the number of colorectal cancer survivors increases, understanding the long term multimorbidity trajectory is critical for improved survivorship care.
Body weight response with anamorelin in advanced non-small cell lung cancer (NSCLC) patients with anorexia/cachexia: Pooled analysis of two phase III trials.
Authors: Currow David Christopher , Temel Jennifer S. , Abernethy Amy Pickar , Friend John , Giorgino Ruben
Published: September 2018

10097

Background: Anorexia/cachexia commonly occurs in patients with advanced NSCLC and is associated with increased morbidity and mortality. In two randomized, double-blind, placebo-controlled phase 3 trials in NSCLC patients with cachexia, the ghrelin receptor agonist anamorelin was well tolerated and significantly increased body weight, lean and fat mass, and anorexia/cachexia symptom burden over 12 weeks compared to placebo (Temel J. Lancet Oncol. 2016). Since an involuntary weight loss of ≥ 5% is an established diagnostic criterion for cancer anorexia/cachexia, an analysis was conducted to assess the proportion of patients with ≥ 5% increase in body weight. Methods: NSCLC patients [ROMANA 1 (NCT01387269; N = 484) and ROMANA 2 (NCT01387282; N = 495)] with stage III/IV disease and cachexia (BMI < 20 kg/m2 or ≥ 5% weight loss during prior 6 months) were randomized 2:1 to receive 100 mg once daily oral anamorelin or placebo up to 12 weeks. A pooled analysis was conducted post-hoc in the modified intent-to-treat population (N = 829) to measure the proportion of patients with ≥ 5% increase in body weight at the end of study (or last observation carried forward since week 6 or 9). Results: The percentage of patients with ≥ 5% increase in body weight at the end of study was significantly higher in the anamorelin arm (N = 188/552, 34.1%) compared to placebo (N = 37/277; 13.4%). Among patients with BMI < 20kg/m2 at baseline (N = 182), 47.3% (N = 53/112) of anamorelin patients had a weight increase of ≥ 5% compared to 17.4% (N = 12/69) in the placebo arm. In both cases the nominal p-value was lower than 0.0001. Conclusions: Data from two published large pivotal studies in advanced NSCLC patients with anorexia/cachexia suggest that anamorelin treatment effect size on body weight is clinically relevant, as shown by the higher response rate achieved when the stringent cut-off of ≥ 5% weight gain was applied. The proportion of patients with BMI < 20kg/m2 that benefited from anamorelin treatment was greater than the proportion of patients who benefited in the entire study sample, suggesting that patients with more advanced cachexia may still benefit from anamorelin treatment. Clinical trial information: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.
Clinical application of comprehensive next generation sequencing in the management of metastatic cancer in adults.
Authors: Cobain Erin Frances , Robinson Dan R. , Wu Yi-Mi , Everett Jessica , Rabban Erica , Kumar Chandan , Schuetze Scott , Alva Ajjai Shivaram , Chugh Rashmi , Worden Francis P. , Zalupski Mark , Tomlins Scott A. , Ramnath Nithya , Schott Anne F. , Stoffel Elena Martinez , Smith David C. , Kunju Lakshmi Priya , Hayes Daniel F. , Talpaz Moshe , Chinnaiyan Arul M.
Published: September 2018

101

Background: Next generation sequencing (NGS) platforms are frequently utilized in the care of patients (pts) with metastatic cancer to identify tumor genomic alterations that may serve as therapeutic targets. Biomarker driven clinical trials, such as NCI-Molecular Analysis for Therapy Choice (MATCH) and Targeted Agent and Profiling Utilization Registry (TAPUR) have augmented clinicians’ ability use this strategy in clinical practice. Methods: From 2011-2015 over 500 adult pts with metastatic solid tumors of diverse lineage underwent biopsy for whole exome and transcriptome sequencing of tumor and matched normal sample through the Michigan Oncology Sequencing Center (Mi-Oncoseq). Genomic alterations identified were reviewed at Precision Medicine Tumor Board and tiered according to their clinical relevance. Alterations were also classified as being identifiable or not identifiable by a commercially available NGS assay such as Oncomine Focus or FoundationOne. Results: Genomic alterations identified by Mi-Oncoseq provided rationale for enrollment in a clinical trial in 72% (n = 360) of cases. The percentage of pts who did receive therapy informed by NGS results increased over time (5% in 2012 versus 11% in 2015). 11% of pts (n = 55) had a pathogenic germline variant (PGV) conferring increased cancer risk identified, none of which were known prior to study entry. Numerous pts had clinically relevant molecular alterations identified by Mi-Oncoseq that would not have been identifiable utilizing targeted NGS assays, including PGVs and activating/deleterious gene fusions. Conclusions: Comprehensive NGS, including DNA and RNA sequencing, readily identifies potentially actionable alterations in the vast majority of pts beyond what is observed with use of targeted NGS platforms. Observed modest increase in utilization of NGS results to direct subsequent therapy over time is due to clinician employment of this strategy earlier in the therapeutic algorithm, increased availability of biomarker driven clinical trials and changes in physician referral patterns. Comprehensive NGS identified many unanticipated PGVs of clinical importance for pts and their families. Clinical trial information: HUM00067928.