bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of intermediate clinical endpoints (ICE) as a primary efficacy endpoint in malignant melanoma.
Authors: Narayanan Siva , Shao Dong , Shah Anshul , Ramesh Vidya 
Published: September 2018

e21075 Background: Melanoma incidence in the US has seen a considerable increase, from 17.8 (1997) to 24.0 (2013) per 100,000, with localized melanoma accounting for 84% of all cases. Early detection and treatment can improve outcomes considerably, resulting in a 99% survival rate. The FDA, within its accelerated approval program, accepts ICE as a primary endpoint, shortening time for patient access to life saving medications. Our objective was to study use of ICE as a primary endpoint for therapies targeting non-metastatic/early-stage malignant melanoma. Methods: A systematic review was conducted in PubMed to identify clinical trials using ICE as a primary endpoint in early stage (non-metastatic, stage I or II) malignant melanoma. An additional search was conducted in clinicaltrials.gov to identify ICE as a primary endpoint in on-going malignant melanoma trials (assess evidence body being built). Searches were limited to the English language, between November 2011 and October 2016. Studies reporting only overall survival (OS) as the primary endpoint were excluded. Results: Of the 226 titles and abstracts screened from PubMed, seven trials were included in the analysis. Of 440 records screened from www.clinicaltrials.gov, one was included, resulting in eight studies of randomized phase 3 trials. Relapse-free survival (RFS) and disease-free survival (DFS) were reported in 3 trials each, and represent the most frequently reported primary ICE (38% each). RFS/DFS is defined as the time from randomization to recurrence of disease or death, and combined, encompass 75% of reported ICE. Other ICE reported were distant metastasis free interval (DMFI, 1 trial) and lymphnode field relapse (1 trial). One trial reported OS as a co-primary endpoint. Conclusions: Definitions of the most observed ICE in malignant melanoma, namely, RFS and DFS, appear to overlap, warranting further investigation into consolidation of outcomes to better assess the value of intermediate endpoints in early stage malignant melanoma. Findings indicate a slow, but growing body of evidence supporting ICE as a primary endpoint in malignant melanoma, bringing focus to prevention or delay of disease progression to alleviate patient burden.
Interleukin-2 (IL-2) and 5-(3,3-dimethyle-1-triazeno) imidazole-4-carboxamide (DTIC) for adjuvant therapy in resected high-risk primary and regionally metastatic melanoma.
Authors: Gosain Rahul , Gill Amitoj , Gragg Hana , Bycroft Ryan Glenn , Rai Shesh , Pan Jianmin , Chesney Jason Alan , Miller Donald M. 
Published: September 2018

e21076 Background: High-dose interferon (IFN) and ipilimumab currently are the only approved adjuvant therapies for high-risk melanoma patients. We analyze the recurrence free survival (RFS), overall survival (OS), and toxicity profile of Interleukin-2 (IL-2) and 5-(3,3-Dimethyle-1-Triazeno) Imidazole-4-Carboxamide (DTIC) combination for resected high-risk primary and regionally metastatic melanoma patients as an alternative adjuvant therapy. Methods: Patients with stage IIB, IIC and stage III melanoma that were treated and received adjuvant IL-2/DTIC combination therapy at a single institution in the year 2000 to 2010 were retrospectively reviewed. No evidence of residual disease was noted prior to therapy. Regimen consisted of subcutaneous IL-2 at 12 x 106 units on days 1 through 4 every month and DTIC 750mg/m2 on day 1 of each cycle every 28 days for 6 cycles. Individual medical records were accessed to collect the data and the Kaplan-Meier method was used to estimate RFS and the OS. Results: Of the 112 patients included, all underwent surgery and then received adjuvant treatment. 109 patients were followed and 3 were lost to follow-up. 59% of the patients were male, 41% were female. 79 (70.5%) of the patients were alive at the time of analysis and 57 patients were currently event free. 69 (61.61%) of the patients completed all 6 months of adjuvant combination treatment with 22.3% of the patients requiring DTIC and 15.2% of the patients’ required IL-2 dose reduction. 2-year OS (from the day of surgery) was 92.85% (95% CI of 86.29-96.53) with RFS of 66.31% (95% CI of 56.92-74.49) and 5-year OS was 75.57% (95% CI of 64.72-83.50) with RFS of 53.05% (95% CI of 41.91-62.58). Conclusions: With little improvement in the RFS from IFN and high toxicity profile with ipilimumab, neither of these treatment regimens seem to be an ideal option. In our retrospective analysis, combination therapy with IL-2/DTIC appears to be beneficial and well tolerated as an alternative adjuvant treatment for patients with high-risk melanoma, but this observation requires further prospective validation.
Patient centered outcomes for skin cancer treatment: A single day Delphi process to assess the importance of treatment themes to a representative panel of skin cancer patients.
Authors: Maher Ian , Alam Murad , Bordeaux Jeremy S , Cartee Todd , Baum Christian , Rossi Anthoy , Lawrence Naomi , Behera Anit , Armbrecht Eric S. 
Published: September 2018

e21079 Background: Increased emphasis is being placed on patient centered outcomes. There is little existing literature on the patient population's prioritization of outcomes in skin cancer care. A PCORI-supported Patient Outcomes Summit was organized to address this. Methods: Patients were recruited from patient support groups, solicitation of ASDS member practices, as well as personal recruitment of patients from the practices of the investigators. A one-day Patient Outcome Summit was convened in Arlington, VA in August 2016. Patients attendees were given orientation to existing outcomes for skin cancer as well as the Delphi process. They then participated in a two round Delphi process by run non-physician facilitators (AB and EA). Group discussion was used to solicit outcomes for inclusion in the rating rounds. Outcomes were then rated anonymously on a 1 (lowest relevance) to 9 (highest relevance) scale. Patients were then able to view the anonymous feedback of the group and rerate the items as they deemed fit based on the group feedback. Results: 21 patients participated in the Delphi process (5 men and 21 women). 10 were melanoma and 11 were non-melanoma patients. 56 treatment related outcomes and themes were identified. The ten most highly rated themes are shown in the table. Conclusions: The first ever skin cancer patient outcome summit was convened to address the lack of patient-centered data in the skin cancer literature and guide measure development. Some traditional outcomes (recurrence) were identifiend. However, the majority of the themes rated most important by the patient attendees center around inclusion of the patient in the decision making process and the physician-patient communication. Increased emphasis and education in these domains may drive increased patient satisfaction in skin cancer care. [Table: see text]
Setting and timing of end-of-life care in cancer patients.
Authors: De Carlo Elisa , Gerratana Lorenzo , Cinausero Marika , Vitale Maria Grazia , Buoro Vanessa , Bonotto Marta , Ermacora Paola , Sacco Cosimo Stanislao Pio , Puglisi Fabio , Fasola Gianpiero 
Published: September 2018

e21502 Background: Limited data are available on how the setting and timing of palliative care (PC) referral can affect end-of-life (EoL) care and survival in cancer patients (pts). The aim of our study was to evaluate the impact of PC referral (hospice and/or home-care services) versus family physician care (FP-C), in terms of both EoL quality of care and survival in cancer pts. Methods: The study included 337 cancer pts who died between January 2015 and February 2016. We retrieved data on type of EoL care and on poor quality of care indicators in the last 30 days of life. Palliative Care Survival (PCS) was defined as the interval between timing of PC referral and death. The survival after treatment (Treatment-Free Survival, TFS) was defined as the interval between the last administration of anticancer therapy and death. Results: FP-C court included 89 pts and PC services court 248 pts. The 248 PC pts were divided in three groups: 99 assisted by both PC services, 58 only by home-care and 91 only by hospice care. The median PCS was 24 days. TFS was significantly longer for the three groups assisted by PC (105, 95, and 82 days respectively) than for that assisted only by FP-C (49 days, p < 0.0001). Compared to PC services, FP-C was associated with higher frequency of poor quality of care indicators, such as emergency room visits (p < 0.0001), hospitalizations (p < 0.0001), hospital death (p < 0.0001) and chemotherapy administration (p < 0.0001). In addition, earlier PC referral (30-60 and > 60 days before death) versus late referral ( < 30 days before death) was associated with a lower frequency of poor quality indicators. Variables such as age, sex and primary tumor were not associated with a different quality of care. Conclusions: Pts referred to PC services, compared to pts referred only to FP-C, had improved EoL survival and quality of care. A better definition of PC referral timing can affect the quality of EoL care in cancer pts.
A practical clinical score to predict early death after a comprehensive geriatric assessment (CGA) in elderly cancer patients: A prospective cohort study with 608 patients.
Authors: Telles O Lima Jurema , Bergmann Anke , Mello Maria Julia Gonçalves , Cavalcanti Zilda , Bezerra Mirella Rebello , Sales Letícia telles , Thuler Luiz Claudio Santos 
Published: September 2018

e21537 Background: Components of the comprehensive geriatric assessment (CGA) correlate with risk of early mortality in elderly cancer patients (ECP). However, its complexity and the time required for its administration. The aim of this study was to determine the impact of each CGA domain on overall survival(OS) and to first step for the development of a prognostic scoring system to stratify ECP. Methods: a prospective cohort study. Participants with a recent diagnosis of cancer were from eight hospitals and one cancer center in Brazil and were recruited during their first medical appointment at the outpatient oncologic clinic. A basal CGA was done before the care decision (ADL, Charlson Comorbidity Index- CCI, Karnofsky Performance status – KPS, GDS15, IPAQ, MMSE, MNA, MNA-SF, PS, PPS, Polipharmacy, QLQc30, TUG). During the follow up of six months, information about the treatments performed and early death was collected. OS was estimated using the Kaplan–Meier method, and survival curves were compared using the Log rank test for categorical variables. A multivariate Cox proportional hazards model was used to select early death risk factors. A clinical score considering the number of risk variables was created. Results: From 2015-2016, 608 ECP, mean age 71.9 (SD ±7.4; range 60-96), 50.7% male, were enrolled. 100 (16.4%) ECP died in less than six months of follow-up. In our multivariate model, controlled by age, site of cancer and cancer stage, the remaining significant risk factors were malnutrition/nonutrition determined by MNA (HR 3.3, 95%CI 1.81-5.99, p < 0.001), KPS < 50% (HR 2.44, CI 1.56-3.81, p < 0.001) and CCI > 2 (HR 1.6, CI 1.09-2.52, p = 0.018). The risk for early death according to the number of risk variables: three (HR 12.99, CI 5.69-29.60, p < 0.001), two (HR 5.65, CI 2.61-12.24, p < 0.001) or one (HR 2.7, CI 1.28-5.87, p = 0.009). Conclusions: a practical clinical score using three instruments of the CGA (MNA, KPS and CCI) can predict independent the risk for an early death in ECP. The development of a practical system for risk scoring, incorporating few clinical prognostic factors, helps to stratify patients into risk groups and to plan a personalized care.
Prospective validation of a novel geriatric screening tool, the Korean cancer study group geriatric score (KG)-7, in older patients with advanced cancer undergoing 1st line palliative chemotherapy.
Authors: Kim Jin Won , Kim Se Hyun , Lee Yun-Gyoo , Hwang In Gyu , Song Hong-Suk , Koh Su-Jin , Ko Yoon Ho , Shin SeongHoon , Woo In Sook , Hong Soojung , Kim Tae Yong , Baek Ji Yeon , Kim Hyun Jung , Kim Hyo Jung , Lee Myung Ah , Kwon Jung Hye , Hong Yong Sang , Ryoo Hun-Mo , Lee Kyung Hee , Kim Jee Hyun 
Published: September 2018

e21540 Background: Full geriatric assessment is time-consuming and labor intensive, and most screening tools were developed in Western countries, which cannot reflect differences in some domains such as nutrition deficit, in Asians. Methods: This prospective study to validate a novel geriatric screening tool, the Korean Cancer Study Group Geriatric Score (KG)-7, was conducted as a substudy of a multicenter study for the prediction tool of toxicity in older cancer patients receiving 1st line chemotherapy (KCSG PC13-09). Abnormal GA was defined as deficits in at least 2 out of 6 domains [activities of daily living (ADL), Korean-instrument ADL (K-IADL), Mini-Mental Status Examination in the Korean version of the Consortium (MMSE-KC), Short-Form Geriatric Depression Scale (SGDS), the Mini Nutritional Assessment (MNA), Timed Get Up and Go test (TGUG)]. KG-7 questionnaire was answered before full GA. We compared the performance of KG-7 with G-8 score, obtained from MNA, by calculating AUC of accuracy, and also sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV). Results: Baseline GA and KG-7 results of 301 patients were collected. Median age was 75 years old (range 70-93). Eighty six (28.6%) and 124 patients (41.2%) showed dependent ADL and IADL, respectively. Impairment for domains of MMSE, SGDS, MNA, and TGUG was identified in 166 (55.1%), 132 (43.9%), 230 (76.4%), and 52 patients (17.3%), respectively. Abnormal GA was documented in 221 patients (73.4%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, the AUC was 0.741 (95% CI, 0.683-0.800), and the SE, SP, PPV, and NPV were 75.6%, 58.7%, 84.3%, and 44.9%, respectively. Abnormal KG-7 score was shown in 198 patients (66.9%). With the ≤ 14 cut-off value of G-8 for abnormal GA, the G-8 showed a SE, SP, PPV, and NPV of 93.6%, 28.0%, 79.2%, and 60.0% with AUC of 0.766 (95% CI, 0.703-0.829). Abnormal G-8 score was shown in 260 patients (88.1%). Conclusions: KG-7 could identify patients with abnormal GA with comparable performance with G-8 and can be a useful screening tool for Asian countries with limited resources and high patient volume.
Association between health status and social integration/loneliness in survivors of adolescent and young adult (AYA) cancers.
Authors: Huang I-Chan , Jones Conor , Srivastava Deo Kumar , Hudson Melissa M. , Robison Leslie L. , Krull Kevin R. 
Published: September 2018

e21563 Background: AYA cancer survivors are at risk of various adverse health outcomes, but the relation between health status, social integration (i.e., social network and support) and loneliness is understudied. Methods: 102 AYA survivors (mean age = 25 years; diagnoses = leukemia 27%; lymphoma 24%; brain tumors 9%; solid tumors 41%) and 102 age-sex-matched controls were recruited from a community-based online panel. Participants reported social network information (e.g., contact frequency, resources for health counseling) for up to 25 of closest friends/relatives, which was used to create a functional social network index. UCLA Loneliness Scale, Duke-UNC Functional Social Support Questionnaire and PROMIS Health Profile were used to measure loneliness, social support and health-related outcomes (physical functioning, depression, anxiety, fatigue and pain), respectively. Multiple linear regression was used to compare functional social network, social support and loneliness between survivors and controls, and to assess the relation between health outcomes and perceived loneliness. Results: Compared to controls, survivors of lymphoma (b = 1.98; p = 0.005), leukemia (b = 1.67; p = 0.012) and solid tumors (b = 1.22; p = 0.030) had a higher functional social network index. However, social support did not differ between survivors and controls (p’s > 0.05). Brain tumor survivors (b = 15.65; p = 0.006) and solid tumor survivors (b = 10.83; p < 0.001) had more loneliness than controls. Compared to low loneliness controls, high loneliness survivors had significantly lower physical functioning (b = -7.72; p < 0.001) and higher anxiety (b = 8.35; p < 0.001), depression (b = 10.57; p < 0.001), fatigue (b = 5.52; p = 0.011) and pain (b = 6.37; p < 0.001) after adjusting for age, sex, education, social integration, and number of self-reported chronic health conditions. Conclusions: Loneliness is significantly associated with poor health-related outcomes in AYA survivors, which is independent of the influence of social integration. Future research is warranted to understand the relation between health status and social interactions among AYA survivors to inform intervention-based strategies.
Utility of a novel smartphone application for breast cancer survivors.
Authors: Kell Malcolm R. , Barry Mitchell 
Published: September 2018

e21577 Background: Breast cancer survivorship aims to improve quality of life and reduce the risk of relapse after diagnosis and treatment. Smartphone applications are now widely used and facilitate many daily activities. Excercise and diet are key components of survivorship and modification of both can improve longterm breast cancer outcome. We have developed a smartphone application focused on enhancing excercise and diet following breast cancer diagnosis; Breast Cancer Survivor. Methods: A Smartphone application was developed with Portable Medical Technology, Ireland (https://itunes.apple.com/ie/app/breast-cancer-survivor/id1043485265?mt = 8). We focused on improving excercise and caloric balance to reduce body mass index. The appliction measured excercise, intensity and distance, to calculate individual energy expenditure and set a target aimed at reducing BMI by 10% over 8 weeks. In additon to excercise we gave dietry advice to focus on caloric intake. We have examined both national and international usage of the application after it was realeased free of charge, for the initial 6 months after release. Results: 770 users donwloaded and used Breast Cancer Survivor in the initial 6 months. Majority of users were in Ireland (38% n = 534), United Kingdom (24.6% n = 339) and United States of America ( 10.7% n = 147). 1376 session of use were recorded and off these 44.2% (n = 608) were return users. BCS app was used for an average of 2.2 minutes per session.Following initial release and local media coverage usage peaked at 401 sessions and then plateaued at 118 sessions after 6 months with only social media coverage. Conclusions: Smartphone application is an effective lifestyle modification, targeting breast cancer survivors. Breast Cancer Survivor has been widely used with only limited promotion. Breast cancer survivorship can be promoted with a smartphone application.
Metastatic Breast Cancer Collateral Damage (MBCCD) project: Addressing unique needs and identifying patients at highest risk.
Authors: DeHart Jessica Noelle Clague , Stanton Annette , Eshraghi Leah , Cooper Ortner Heather , Williamson Timothy , Jorge Alexandra , Obidegwu Nwamaka , Love Susan M. 
Published: September 2018

e21592 Background: From The Health of Women (HOW) Study™, we found that participants living with metastatic breast cancer (MBC) had a considerably diminished quality of life (QoL) compared to those with less advanced breast cancer. When faced with MBC, managing and minimizing collateral damage (CD) resulting from sequential and often continuous treatments is crucial to improving QoL. The aim of the MBCCD Project was to characterize the unique experience of MBC in order to identify and address potential areas of need in this underserved population. Methods: We crowdsourced input and gathered free-text data from 353 MBC patients to document the breadth of CD affecting QoL. We then developed a new questionnaire using validated QoL scales and PROMIS measures, along with a novel assessment of Living with MBC derived from the crowdsourcing data, which, in some cases, included verbatim statements from patients. Results: Among the 515 MBC respondents, the median age was 57 years (28-86 years), and the majority was female (99%) and non-Hispanic White (91%). Patients retrospectively reported a significant decline in overall QoL after MBC diagnosis (Before MBC: 51% excellent and1% poor/extremely poor; After MBC diagnosis: 12% excellent and15% poor/extremely poor; p < 0.05). As expected, considerable CD was reported in every aspect of the patients’ lives—physical, social, financial and psychological. MBC patients who were younger ( < 50 years), had lower financial status, and/or reported having children under the age of 18 years living at home were identified as being at highest risk of significant CD in every category (p < 0.05). Contrary to common belief in the clinical setting, CD did not vary as a function of treatment type or metastatic location. Conclusions: Findings illustrate the need for dynamic and personalized strategies targeting CD to improve the health and well-being of MBC patients. Within each area of CD, critical needs and subsets of patients at highest risk were identified. Next steps include increasing diversity and working with MBC advocates and provider-survivor collaborators to develop recommendations that maximize benefit to MBC patients while remaining feasible for providers.
Does screening for anxiety and depression efficiently identify patients who want help?
Authors: Jacobs Linda A. , Blauch Abigail N. , Pucci Donna A. , DeMichele Angela , Palmer Steven C 
Published: September 2018

e21604 Background: Screening cancer patients for psychosocial difficulties is recommended as a means of identifying individuals in need of assistance and improving outcomes. Although screening may identify individuals at risk for difficulties, it is unclear if screening a) identifies those willing to accept assistance or b) may have the consequence of rationing care away from those who want assistance but screen negatively. We examined these issues in a sample of breast cancer (BC) survivors. Methods: Consecutive non-metastatic BC survivors > 1 year from end of treatment completed an online assessment including the Hospital Anxiety and Depression Scale and patients' desire for assistance with Anxiety and Depression prior to their survivorship visit. Results: Participants (N = 260) were predominately white (81.5%), college educated (81.2%), married/partnered (74.6%), and had an annual income of $60,000 or greater (69.3%). Most were diagnosed Stage I (48.3%) or Stage II (33.5%) BC, and underwent surgery (100%), chemotherapy (60.9%), and/or XRT (70.1%). Mean depression (M = 3.89; SD = 3.73) and anxiety (M = 6,63; SD = 4,47) scores were low and below the established cut point of 8 (all t > -5.0; all p < .001 ), although 20.7% and 42.3% screened positively for depression or anxiety, respectively. Screening positive for depression or anxiety was significantly associated with a desire for intervention (all X2> 22.0; all p < .001 ). However, only a minority of those screening positive for depression (32.1%) or anxiety (34.5%) desired intervention. The number of individuals screening negative but desiring intervention compared to those screening positive and desiring intervention was 76% for depression and 50% for anxiety. Conclusions: Most BC survivors screening positive for depression or anxiety do not desire intervention, at least within the cancer setting. In absolute numbers those screening negative, desire intervention relative to those screening positive at rates of 50-76%, representing a missed opportunity to improve outcomes. Screening without exploring desire for intervention may over identify individuals who do not desire help while missing a relatively large number of those who possibly may.