bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune gene expression and bayesian network analysis in advanced non small cell lung cancer (NSCLC) patients treated with immunotherapy.
Authors: Baglivo Sara , Bianconi Fortunato , Tofanetti Francesca Romana , Ricciuti Biagio , Pistola Lorenza , Siggillino Annamaria , Reda Maria Sole , Mencaroni Clelia , Currà Maria Francesca , Teti Valeria , Metro Giulio , Bellezza Guido , Minotti Vincenzo , Roila Fausto , Ludovini Vienna
Published: May 2019

e20693

Background: Immune checkpoint inhibitors (ICIs) have revoluzionized the therapeutic paradigm for different types of cancer including NSCLC. Clinical benefit, however, is limited to a minority of patients. The only adopted predictive biomarker, PD-L1 IHC testing, suffers from some limitations. A better understanding of biomarkers associated with response to ICIs is needed. Here, we studied immune gene expression profile and association with clinical response to immunotherapy in advanced NSCLC patients (pts) treated with ICI. Methods: A total of 37 Formalin-fixed, paraffin-embedded (FFPE) samples from advanced NSCLCs were analyzed by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) (ThermoFisher Scientific) to measure the expression level of 395 genes associated with 36 functional groups including checkpoint pathways, lymphocyte regulation and cytokine interactions, using the Ion Chef and Ion Torrent PGM. Gene level differential expression analysis were performed with the Torrent Suite and Transcriptome Analysis Console (TAC) 4.0 Software. Gene network analysis based on Bayesian algorithm was performed by GeneMANIA database querying with the genes selected through mRNA expression analysis. Results: Among 37 FFPE samples only 18 showed more than 300 OIRRA detectable target genes. In this subgroup, gene expression analysis revealed 7 genes (CCR2, CRTAM, FASLG, SELL, TIGIT, TNFRSF4, and TP63) up-regulated and one gene (CXCL8) down-regulated (p-value < 0.05) in ICI-responders compare to ICI-no responders. Bayesian enrichment computational analysis of the eight gene expression signature showed a more complex network which involves other 10 genes (SIRPG, GZMK, XCL2, CD8A, CD2, IFNG, SIT1, TAGAP, PTPRC and GZMH), correlated with different functional groups. Three main immune-pathways were identified (p < 0.01) (T cell activation, leucocyte activation and migration) involving TIGIT, TNFRSF4, CCR2 and CXCL8 genes among the gene expression signature identified. Conclusions: Our results revealed an immune response gene expression signature of 8 genes differentially expressed between ICI and ICI-no responders. Cancer systems biology analysis approach strengthen our findings identifying an immune molecular network and confirm the correlation of the gene expression signature with relevant immune regulatory functions. If validated, our results may have an important role for the development of a robust test to select patients properly and predict immune response to enable precision immunotherapy.
Demoralization and associated features in an Italian sample of end-of-life cancer patients.
Authors: Airoldi Mario , Bovero Andrea , Botto Rossana , Adriano Beatrice , Opezzo Marta , Tesio Valentina , Torta Riccardo
Published: May 2019

e23004

Background: Demoralization is an expression of cancer-related existential distress that emerges from feelings of loss and changes linked to a life-threatening clinical condition. It is characterized by subjective incompetence, sense of failure, hopelessness, loss of purpose/meaning and low self-esteem. The study aimed to explore prevalence, latent dimensions and associated features of demoralization in a sample of end-of-life cancer patients. Methods: Participants were recruited for a cross-sectional assessment. For each patient, demoralization, anxiety, depression, physical symptoms, pain, spiritual well-being, and dignity were evaluated through validated rating scales and personal and medical data were gathered by a clinician. Final sample consisted of 235 end-of-life cancer patients with a Karnofsky Performance Status (KPS) lower than 50 and a life expectancy of few weeks. Results: High levels of demoralization occurred in 22.6% (n = 53) of patients. Sixty-four participants (27.2%) had low demoralization and 50.2% (n = 118) had moderate demoralization. Emotional Distress and Inability to Cope, Loss of Purpose and Meaning, Worthlessness, Sense of Failure and Dysphoria were the five latent dimensions of demoralization emerged from the factor analysis. Demoralization was significantly associated with depression, anxiety, dignity, spiritual well-being and the physical symptoms except for nausea and breathing problems. Conclusions: Demoralization levels seem to be higher in this distinctive population than in advanced cancer patients. This could be due to the fact that end-of-life cancer patients are in a severe clinical condition and nearing death. The emerged demoralization dimensions could be five forms of expression of the existential distress typical of this illness phase. The considerable number of patients suffering from demoralization strengthen the need for psychological interventions in order to reduce the existential distress at the end of life, focusing on finding meaning and detecting spiritual concerns.
Unscheduled hospitalization in advanced cancer patients: Time to rethink about the illness.
Authors: Ostios-García Lorena , Miranda Poma Jesus , Sánchez Cabrero Darío , Gutiérrez Sainz Laura , Villamayor Sánchez Julia , Alonso-Babarro Alberto , Feliu Batlle Jaime
Published: May 2019

e23007

Background: The aim of our study was to determine if an unscheduled hospitalization in advanced cancer patients is a good time for palliative care referrals, and if this indicator could be improved with some other prognostic score. Methods: We conducted a retrospective study, which included all patients with unscheduled hospitalization in the medical oncology service from January 2011 to December 2013. In order to improve the accuracy of the analysis we considered only first admissions of each patient. We excluded patients with scheduled and unindicated hospitalization. The main variable was survival after an unscheduled hospitalization. We collected the following variables: demographic (age, sex, date of birth, date of death and place of death), tumor type, clinical variables (reason for admission, date of hospitalization, assessment by the palliative care unit during hospitalization, date of last chemotherapy and ECOG), analytical variables (albumin, lymphocytes and lactate dehydrogenase) and a prognostic nomogram developed by our team. Results: Inclusion criteria were met by 1,180 patients. Table summarizes the main sociodemographic characteristics, the type of tumor, and the functional status of patients according to the ECOG scale. After two years of follow-up, 816 (69%) patients had died. The median overall survival was 188 days (161-214). Patients with breast and gynecological cancer had the longest survival, while patients with melanoma, gastric cancer, lung cancer, and pancreatic cancer had the poorest survival. 676 patients (58%) were readmitted during the following year. Readmissions meant a significant decrease of survival. The stage of the oncological disease and performance status measured by ECOG had a clear relationship with survival time. Prognostic nomogram showed high accuracy to predict the probability of survival. Median survival for different quartile was respectively: 348, 139, 68 and 31 days (p < 0´000). Conclusions: The median survival of patients after an unscheduled hospitalization was around 6 months. Been admitted seems a good indicator to introduce specific palliative care. The use of other prognostic scores, as a prognostic nomogram, could help to select patient’ groups with poorer survivals. [Table: see text]
Perceptions of medical status and treatment goal in older adults with advanced cancer.
Authors: Thompson Leah L. , Temel Brandon , Fuh Charn-Xin , Server Christine , Kay Paul , Landay Sophia , Lage Daniel E , Traeger Lara , Scott Erin , Jackson Vicki A. , Greer Joseph , El-Jawahri Areej , Temel Jennifer S. , Nipp Ryan David
Published: May 2019

e23016

Background: Perceptions of medical status and treatment goal are often used to assess prognostic awareness, but whether these items fully capture patients’ understanding of their prognosis remains unclear. We sought to better understand these measures by investigating their relationship with quality of life (QOL), symptom burden, functional impairment, hospitalizations, and overall survival (OS). Methods: We enrolled patients age ≥70 years within 8 weeks of a diagnosis of incurable gastrointestinal cancer. We surveyed patients to assess perceptions of medical status [terminally ill vs not], treatment goal [curative vs non-curative], QOL (EORTC - Elderly Cancer Patients), symptom burden (Edmonton Symptom Assessment System [ESAS]), and functional impairment (activities of daily living [ADLs]). We used regression models adjusted for age, sex, and education to explore relationships between these items and patients’ QOL, symptom burden, functional impairment, risk of hospitalizations, and OS. Results: Of 132 patients approached, 103 (78.0%) enrolled (mean age 77.62 years, 47.6% female). Half (49.5%) reported a terminally ill medical status and nearly two-thirds (64.0%) reported a non-curative treatment goal, with 42.0% reporting discordant responses to these items. Patient report of a terminally ill status was associated with worse QOL (EORTC illness burden: 53.59 vs 35.26, p = .001), higher symptom burden (ESAS score: 28.15 vs 16.79, p = .002), more functional impairment (number of ADLs: 3.63 vs 5.24, p = .006), greater risk of hospitalizations (HR = 2.41, p = .020), and worse OS (HR = 1.93, p = .010). We found no associations between these outcomes and patient-reported treatment goal. Conclusions: In older adults with advanced cancer, half reported a terminally ill medical status and nearly two-thirds reported a non-curative treatment goal. Patient report of a terminally ill status was associated with worse QOL, symptom burden, functional impairment, risk of hospitalizations, and OS. We did not find associations between these outcomes and patient report of their treatment goal. Our findings suggest that these questions measure different constructs and more nuanced tools for assessing prognostic awareness are needed.
Delirium incidence, risk factors, and treatment in older adults receiving chemotherapy: A scoping review.
Authors: Alibhai Shabbir M.H. , Jung Patrick , Alam Zuhair , Yeung Lily , Malik Uzair , Syed Ali Taqi , Rosario Carla , Yokom Daniel , Rowbottom Leigha , Ayala Ana Patricia , Reka Roger , Puts Martine
Published: May 2019

e23025

Background: Older adults with cancer are at increased risk of delirium given their advanced age, multiple comorbidities and medications, prevalence of cognitive impairment, and possibly cancer treatment. Awareness of such risks and interventions to prevent or treat delirium is important to clinicians and to provide high quality care. However, there is scant published information on the risks of delirium with chemotherapy or evidence-based approaches to prevent or treat it. We performed a scoping review to summarize the available evidence. Methods: We conducted a scoping review using the framework of Arksey and O’Malley. We systematically searched peer-reviewed journal articles in English, French, and German from Medline, Embase, PsychINFO, CINAHL Plus, and Cochrane Central from inception until January 2017 to identify studies that examined delirium in patients receiving chemotherapy. We also attempted to identify any studies that reported on multivariable delirium risk prediction models and any clinical trials that examined prevention or treatment of delirium. Article titles and abstracts as well as full text articles were reviewed using Covidence software by two or more reviewers independently. Similarly, data extraction was performed by two independent reviewers. Results: A total of 21,678 titles and abstracts were screened, and 1,166 full-text articles were reviewed. Nineteen articles with varying study designs (retrospective administrative databases to clinical trials) reported on delirium using an acceptable diagnostic standard. Sample sizes varied from 15 to over 21,000. No one tumour site or treatment protocol constituted the majority of studies. The incidence of delirium ranged from 0 to 51% (mean 13.5%). The time course of delirium relative to the cycle of chemotherapy was inconsistently reported. No studies reported on risk prediction models for delirium, and no intervention studies to prevent or treat delirium were identified. An additional 109 studies reported on outcomes that could be part of the delirium syndrome but did not meet even our broad inclusion criteria (e.g. cognitive disturbance). Conclusions: Delirium may occur in over 1 in 8 older adults receiving chemotherapy, although there were substantial limitations in reported studies. This scoping review highlights the dearth of knowledge in the area, particularly for risk factors, prevention, and treatment, and emphasizes the need for high-quality studies examining these important outcomes in the oncology setting.
Comparison of mortality trends in geriatric and nongeriatric patients with salivary gland tumors.
Authors: Nawaz muhammad Sarfraz , Parikh Jigarkumar R. , Guddati Achuta Kumar
Published: May 2019

e23026

Background: The treatment of salivary gland tumors has not changed significantly in the past two decades. However, its increased incidence in the geriatric population poses new challenges for their management. This study explores the incidence-based mortality (IBM) trends in the geriatric and non-geriatric population for the time period of 2000 to 2014 and compares the trends between races. Methods: Mortality data was extracted from the Surveillance, Epidemiology, and End Results (SEER) Database for the years 2000 to 2014. IBM for all stages of salivary gland tumors was queried and the results were grouped by age (geriatric vs. non-geriatric) and race (Caucasian/White, African American (AA)/Black, American Indian/Alaskan native and Asian/Pacific Islander). All stages and both genders were included in the analysis. T-test was used to determine statistically significance difference between various subgroups. Linearized trend lines were used to visualize the mortality trends between various subgroups (Geriatric vs. Non- geriatric and Caucasian vs. African American). Results: IBM for salivary gland tumors has worsened since 2000 to 2014 for both geriatric and non-geriatric patients (P < 0.05), There was a statistically significant difference between these two groups in both Caucasian/White and AA/Black patients. Notably, the worst IBM rates were noted in non-geriatric AA/Black patients followed by non-geriatric Caucasian/White patients. However, there was no statistical difference in IBM between geriatric patients of Caucasian/White and AA/Black descent. Conclusions: The similarity in IBM for geriatric patients with salivary gland tumors in both Caucasian/White and AA/Black groups suggest that the effects of race may not be pronounced in the elderly population. The high rate of IBM in non-geriatric AA/Black patients may suggest environmental influence and warrants further study.
Treatment approaches and survival outcomes of older patients with locally advanced esophageal cancer (LAEC) in Ireland.
Authors: Martin Petra , o'Leary Eamonn , Deady Sandra , Horgan Anne M.
Published: May 2019

e23034

Background: Neo+/- adjuvant treatment data in older patients with cancer is sparse due to exclusion of this population from clinical trials. We evaluated the management of locally advanced esophagogastric cancer (LAEC) in older Irish patients to determine treatment modalities utilized and identify factors associated with survival. Methods: Patients diagnosed with LAEC (stage II or III) over a 5 year period (2007-2011)were identified from the National Cancer Registry of Ireland. Follow-up was till end 2014.Demographic characteristicswere assessed. Treatment was classified as “best supportive care (BSC)”, “surgery only”, “neo/adjuvant treatment” and “chemo/radiation alone” (ie chemo, radiotherapy or chemoradiotherapy alone in the absence of surgery).Survival was estimated by Kaplan-Meier estimates and Cox models. Clinicopathologic factors and treatment type found to be significant in univariate analysis were included in a multivariate analysis (MVA). Results: 46%(n = 580) of the 1,251 patients were ≥70yrs, 62% had stage III disease and 51% had gastric cancer. 11% (n = 134) received BSC, 23% (n = 288) had surgery only, 31%(n = 390) had chemo/radiation alone, 35% (n = 439) had neo/adjuvant treatment. 20% (n = 39) of patients ≥75yrs had neoadjuvant treatment compared to 46% < 75 yrs. No patient ≥80yrs received neo/adjuvant treatment. With increasing age patients were less likely to receive neo/adjuvant treatment (p < 0.001), less likely to receive surgery (p < 0.001) and less likely to receive any treatment (p < 0.001).Median survival(OS) decreased with age (< 70yrs: 23months; 70-74: 19months; 75-79:13months; ≥80 years:10 months). In MVA, older age, smoking, later stage, higher grade were significantly associated with a higher risk of death.Including an interaction between treatment and age, patients receiving adjuvant or neoadjuvant treatment had lower risk of death than any other treatment group regardless of age. Conclusions: Older patients were less likely to receive any treatment for LAEC than younger patients. Patients ≥70 years benefit from neo/adjuvant treatment, however,these patients are often excluded based on age. Prospective clinical trials focusing on elderly patients and incorporating life expectancy, comorbidities and geriatric assessment are needed to best guide treatment.
Validation of G8 and its acuracy as a predictor of object in oncological patients with age of ≥ 60 YEARS. prospective cohort of 889 brazilian elderly cancer patients.
Authors: Telles O Lima Jurema , Viana Raissa , Sales Letícia telles , Rebello Mirella , Figueiroa José Natal , Bergmann Anke , Cavalcanti Zilda , Mello Amanda L LINS , Mello Maria Julia Gonçalves , Thuler Luiz Claudio Santos ,   BROG- Brazilian Research Oncologic Geriatric Group
Published: May 2019

e23036

Background: The G8, a questionnaire with 8 questions, has been specifically developed as a screening tool for vulnerability in older patients (70+) with cancer, with results suggesting 14 points as a threshold (equivalent to 90% sensitivity and 60% specificity). Its prognostic value for early death was not evaluated in Brazilian population. Methods: Cancer patients (60 years or older) with solid organ malignancies were included in a prospective cohort in a Brazilian Geriatric Oncology Clinic, between 2015 and 2017. Before the start of any oncologic therapy, a Comprehensive Geriatric Assessment (CGA) with 12 questionnaires was performed. For this study, we analyzed the G8 (Figure 1) considering items from Mini Nutritional Assessment (MNA), polypharmacy ( > 3 medications per day), self reported health status and the age of patient. G8 score was considered abnormal if ≤14, and early death (within six months of surveillance) was the gold standard for the study accuracy. Cox proportional hazard risk and Kaplan-Meier survival curves were performed. Results: 889 patients were enrolled and there were 145 (16.3 %) early deaths. Overall, 52% were male, the extremes of age were from 60 to 97 (mean 72.5 ± 0.24), and 38% were < 70 years old. The most common cancers were prostate (31.2%), digestive tract (21.9%) and breast (16.0%); 30.4% were metastatic. 470 (52,9%) from all patients had abnormal (≤ 14) G8 score; 128 (27.2%) who had abnormal G8 score died within the first 6 months, versus 17 (4.1%) with normal score (Table 1). At cut point 14, the G8 sensitivity was 88.3% (CI95% 81.9 - 93.0); specificity 54.0% (CI95% 50.4 - 57.7); positive predictive value 27.2% (CI95% 23.3 - 31.5); negative predictive value 95.9% (CI95% 93.6 - 97.5); area under ROC curve was 0.819 (Figure 2). For those older than 70, the G8 sensitivity was 91% (CI95% 83.4 - 96.1). Abnormal scores showed significant differences in survival probability (Figure 3). Conclusions: G8 score is a strong and consistent predictor of overall 6-month survival, regardless of age, metastatic status or tumor site in Brazilian older (60 or older) oncologic patients. This finding strengthens the clinical utility of this instrument in the Geriatric Oncology and may be an option to extend the practice of Geriatric Assessment in countries with medium-low economic development, even in the younger elderly population.
Evaluation of the diagnostic and prognostic performance of the modified G8 screening instrument in oncological patients with age of 60 YEARS or age: Prospective cohort of 889 Brazilian elderly cancer patients.
Authors: Telles Sales Letícia , Telles O Lima Jurema , Rebello Mirella , Figueiroa José Natal , Thuler Luiz Claudio Santos , Bergmann Anke , Orange Flavia , Mello Maria Julia Gonçalves , Camara Davi de brito
Published: May 2019

e23040

Background: Elderly oncology patients are not often included in studies of new therapeutic guidelines. The modified-G8 is easy to use, has satisfactory accuracy and does not require additional tools. Its value for predicting early death has not been evaluated. Objective: To evaluate accuracy of the modified G8 instrument for prediction of early death (up to 6 months) in elderly Brazilian patients (≥ 60 years). Methods: We used data from a prospective cohort with participants aged 60 years or older and a recent diagnosis of a solid neoplasm, followed in a geriatric oncology outpatient clinic between 2015 and 2017. Sociodemographic, clinical and laboratory data were obtained, along with CGA. From the primary data, we developed a modified-G8 score using 6 as the cut-off point, normal being < 6 and abnormal being ≥ 6. The primary outcome was early death (occurring within up to 6 months) considered the gold standard for the accuracy study of modified-G8 as a predictor of early death. Through bivariate and Cox multivariate analysis, the risk for early death (Hazard Ratio - HR crude and adjusted) was determined. Overall survival was estimated using the Kaplan-Meier method, and the log-Rank test was used for comparisons according to the categorization of the scores. Results: Of the 889 participants included, 537 (60%) had modified G8 scores ≥ 6 (abnormal). The overall mean score was 9.9 ± 8.4; mean age was 72,5 years (range, 60–97 years), 38% were 60 and 70 years of age. Fifty-two percent of the participants were male. The most common tumor sites were prostate (31%) and breast (16%), followed by digestive and gynecological (both with 11%). On analysis of accuracy, we found sensitivity 91.7% (95% CI 86–95.7), specificity 45.7% (95% CI 42.1–49.4), positive predictive value 24.8% (95% CI 21.2–28.6) and negative predictive value 96.6% (95% CI 94.1–98.2), area under the ROC curve 81.7% (95% CI 77.9–85.4). The crude HR for early death among those who had abnormal scores was 8.3 (95% CI 4.6–14.9) and the age-adjusted HR, tumor site and metastatic disease at diagnosis was 4.5 (95% CI 2.5–8.3) times greater and survival was lower (log-rank p 0.001). Conclusions: The modified G8 predicted early death in an elderly population (≥ 60 years) with cancer in a northeastern Brazilian institution. Satisfactory prognostic accuracy was obtained. This instrument could reduce the number of patients who would follow-up with CGA, saving time and resources, and accelerating individualized treatment.
Tobacco cessation practices among primary care physicians in northern Illinois.
Authors: Nocon Cheryl , Bhayani Mihir , Karcioglu Amanda
Published: May 2019

e23054

Background: Tobacco cessation is an acknowledged key component of cancer survivorship programs, but significant barriers to program implementation exist. In a 2012 ASCO member survey, 86% of respondents agreed that tobacco cessation should be a routine part of clinical care. However, only 29% reported adequate training. A 2013 survey of physicians at NCI Cancer Centers also showed high levels of support for such programs, but only 1% of oncologists personally engaged themselves. This view is in line with ASCO guidelines that recommend cessation interventions by primary care (PCPs). There is a disconnect between the oncologist’s desire to provide high quality tobacco cessation support for cancer patients and the delegation and delivery of such support. The goal of our study is to evaluate current tobacco cessation practices of PCPs in a large integrated healthcare system. Methods: An electronic survey was sent to all PCPs (n = 165) of the NorthShore Medical Group (Northern Illinois) with questions about their views and practices regarding tobacco cessation. Results: 53 PCPs responded to the survey (response rate of 32%). 94% of respondents believe that PCPs are primarily responsible for addressing tobacco cessation with general patients. 89% believe that PCPs are also responsible for cancer patients, although 34% believe the responsibility should be shared with oncologists. 100% believe that tobacco use affects cancer outcomes in their patients, and 98% report sufficient training in providing cessation support. 90% always ask their patients about tobacco status at the initial visit; this drops to 21% at follow-up visits. For current smokers, 57% of PCPs recommend tobacco cessation all the time and 36% recommend services most of the time. Lack of patient willingness was the most frequently cited barrier to tobacco cessation efforts (74%), followed by lack of time (46%) and lack of resources (42%). Conclusions: PCPs view themselves as primarily responsible for addressing tobacco cessation with their patients but are limited by multiple factors. This primary care-based approach is endorsed by ASCO and other clinical guidelines. More financial and clinical support should be allocated for successful efforts against tobacco dependency.
Real-time detection of patient-reported outcomes (PRO) through an app: A Brazilian experience.
Authors: Morelle Alessandra Menezes , Lima Geraldine Eltz de , D'Agustini Nathalia , Venero Fernando Castilho , Barrios Carlos H.
Published: May 2019

e23059

Background: patient-reported outcomes (PRO) data are critical for informing patient-centered care and have been shown to enhance our ability to communicate with patients and to control their symptoms. Evidence suggests that patient active participation in symptom reporting and prompt attention to management may have a positive and measurable impact in survival. However, PRO data are not commonly collected in routine cancer care due to challenges – cost, technological rigidity of existing electronic health records and misalignment of stakeholders’ incentives. Methods: in an effort to bridge the unmet needs of PRO collection and integration into routine cancer care, we developed a symptom monitoring and management system that was launched as a free mobile app in August, 2018. Tummi app is designed for reporting 28 symptoms based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Symptoms are reported in a 3-point scale (mild, moderate, severe) and patient reported an overall well-being scale represented by emojis. Tummi has the ability to record symptoms, summarize the reporting in physical printout, and automatically store and analyze the input symptoms into graphical interpretations. Results: since august 2018, 1292 patients downloaded and enjoyed the app. Of these, 240 recorded spontaneously their diagnosis. The most common side effect registered was fatigue followed by back pain. Regarding general well-being reports, male patients (25.68%) and female patients (74.32%) totaled 3771 records. Of these, on 50.22% of the time the patients were well, while in 40.17% they were average and in 9.59% they felt bad when made the report. Conclusions: there is an opportunity to better deliver our care for cancer patients, empowering them through collecting their own data. Tummi proved to be doable and understandable for patients’ language in Brazil.
iMETX (Individualized Metabolic RX): An environmental intervention to increase energy expenditure in breast cancer survivors.
Authors: Ballinger Tarah Jean , Althouse Sandra K. , Olsen Timothy P. , Miller Kathy , Sledge Jeffrey
Published: May 2019

e23060

Background: Despite survival and quality of life benefits associated with physical activity (PA), many breast cancer survivors remain inactive. Effective, sustainable PA interventions must account for individual differences in capability, motivation, and environment. iMETX evaluated the feasibility, mechanics, and efficacy of delivering an individualized, dynamic intervention to increase energetic capacity and energy expenditure in breast cancer survivors. Methods: Stage 0-III breast cancer pts who had completed primary treatment were enrolled. Baseline PA patterns were collected using a wearable GPS/accelerometer for 4 weeks pre- intervention. Detailed movement data collection continued throughout the 12- week intervention, during which pts received tailored PA “prescriptions” every 1-3 days from an interactive web application, adjusted based on individual capability and environment to achieve pre- determined energy endpoints. Baseline and post- intervention, energetic capacity was assessed by power generation using a stationary bicycle protocol feasible in the clinic setting over a range of physical capabilities. Body composition by DEXA and quality of life questionnaires were collected. Results: 56 of 57 enrolled pts completed the intervention (98%). Median age was 60 (range 38 – 82), and pts were an average of 5.25 yrs from diagnosis (range 0.5 – 21 yrs). In the total population, energetic capacity (Watts/kg lean mass) increased significantly from 1.75 to 1.99 W/kg (p < 0.01) post- intervention. Separated by baseline energetic capacity, the lowest performing tertile improved significantly (0.76 to 1.12 W/kg, p < 0.01), while the highest performing tertile did not (2.75 to 2.96 W/kg, p = 0.30). Physical and functional well-being also improved (FACT-B TOI, pre: 72.26, post: 74.66, p = 0.02). Conclusions: iMETx is a feasible PA intervention with high adherence rates. Individualized PA prescriptions allowing pts to move in their typical environment resulted in improved energetic capacity and well- being. Results were particularly significant in those with the lowest baseline energetic capacity, a population most in need of effective and accessible PA interventions. Clinical trial information: NCT03158519.
Cutaneous eruption as a prognosis indicator for cancer patients treated with EGFR tyrosine kinase inhibitors: A systematic review and meta-analysis.
Authors: Wang Yensheng , Wu Jennifer , Wang Shi-Yi , Lacouture Mario E. , Wu Mei , Chung Wen-Hung
Published: May 2019

e23063

Background: Clinical symptom is often a direct method to evaluate the treatment effects. With the emergence of EGFR-targeted drugs on market, it is unclear to apply cutaneous toxicity in evaluating treatment effects and outcomes in cancer patients. This study aimed to determine whether adverse skin event as a survival indicator for patients treated with EGFR tyrosine kinase inhibitors. Methods: PubMed, EMBASE, Scopus, trial register and Cochrane Library were searched on November 11, 2018 to identify studies reporting survivals outcomes. The following search/exploded terms were used: “ EGFR-TKIs: gefitinib/erlotinib/afatinib/osimertinib ”, “ cutaneous toxicity”, “ survival”. Two investigators performed study selection independently and assessed risk of bias with ROBINS-I method. Data were pooled with random effects models and further subgroup by cancer types. Funnel plot, Egger test and Begg test were performed for detection of publication bias. Sensitivity analysis was performed by excluding potential outliers. Results: There were 24 studies identified with 4696 patients included. Skin adverse event was found to be significantly associated overall survival rate (HR, 0.48; 95% CI, 0.43-0.53; P < 0.00001; I2 = 83%) and progression free survival rate (HR, 0.59; 95% CI, 0.41-0.85; P= 0.004; I2 = 88%). Subgroup analysis suggested among non-small cell lung cancer patients, skin adverse event was significantly associated with overall survival (HR, 0.39; 95% CI, 0.25-0.60; P < .0001; I2 = 86%) but not progression free survival (HR, 0.65; 95% CI, 0.29-1.45; P= 0.29; I2 = 95%). Among other cancer types patients, skin adverse event was significantly associated with overall survival (HR, 0.59; 95% CI, 0.41-0.84; P= 0.004; I2 = 70%) and progression free survival (HR, 0.61; 95% CI, 0.41-0.91; P= 0.02; I2 = 80%). Begg test and Egger test suggested no evidence of publication bias. Sensitivity analysis also showed similar results. Conclusions: Skin eruption had 52% lower risk of death and 41% lower risk of progression in cancer patients treated with EGFR-TKIs. This association should be further incorporated with cancer survivorship care planning.
Fatigue in long-term survivors of acute promyelocytic leukemia (APL) and its association with other symptoms and functional limitations.
Authors: Efficace Fabio , Breccia Massimo , Avvisati Giuseppe , Cottone Francesco , Intermesoli Tamara , Borlenghi Erika , Carluccio Paola , Rodeghiero Francesco , Fabbiano Francesco , Luppi Mario , Romani Claudio , Sborgia Marco , D'Ardia Stefano , Nobile Francesco , Cantore Nicola , Crugnola Monica , Nadali Gianpaolo , Amadori Sergio , Vignetti Marco , Lo-Coco Francesco
Published: May 2019

e23073

Background: Despite cancer survivorship research for patients with solid tumours is increasing, there is paucity of data for patients with hematologic malignancies. We aimed to: 1) investigate factors associated with development of fatigue in long-term APL survivors; 2) describe prevalence of other key symptoms and functional limitations by fatigue severity. Methods: The current analysis is based on 244 APL survivors with a median follow-up from diagnosis of 14.3 years, who were recruited in a large multicenter study. Fatigue was evaluated with the validated FACIT-Fatigue scale. Multivariate linear regression analysis was used to investigate factors associated with self-reported fatigue and key clinical and treatment-related variables were also considered in the analysis. Patients were also divided into two groups based on the FACIT-Fatigue median score identifying a low fatigue (LF) and a high fatigue (HF) group. Prevalence (i.e., not present, mild and moderate to severe) of key symptoms and functional limitations, measured with the EORTC QLQ-C30, were also analyzed by fatigue severity. Results: Multivariate analysis showed that a lower age at diagnosis (p = .002), absence of comorbidities (p = .001) and a greater social support (p = .004) were independently associated with lower fatigue. Patients in the HF group had a significantly higher prevalence of many symptoms, including: pain (p < .001), dyspnea (p < .001), insomnia (p < .001), appetite loss (p = .010), nausea and vomiting (p = .026) and diarrhea (p = .002) than patients in the LF group. As an example, whilst in the HF group there were 61% of patients also reporting pain (with any level of concern), in the LF group there were only 26% of patients reporting pain. Also, HF patients reported a significantly higher prevalence of functional limitations including: physical, role, social, emotional and cognitive functioning (each with p < .001). Conclusions: Our data provides novel information of factors that are independently associated with fatigue severity in long-term APL survivors. Greater fatigue is also associated with a substantial burden of other symptoms and functional limitations.
The impact of chemotherapy on sleep quality in women undergoing cytotoxic treatment for breast, ovarian, and endometrial cancer.
Authors: Cantillo Evelyn , Beffa Lindsay , Luis Christine , Raker Christina , Robison Katina , Sikov William M.
Published: May 2019

e23077

Background: To determine changes in sleep quality among women with breast, ovarian, and endometrial cancer during chemotherapy and to assess the impact of sleep quality on quality of life (QOL). Methods: A prospective cohort study was performed at The Program in Women’s Oncology among chemotherapy naïve women diagnosed with breast, ovarian, or endometrial cancer scheduled to begin treatment. Ovarian and endometrial patients were combined into one group (Gyn) for analysis. Two validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy (FACT), which measure sleep quality and QOL, respectively, were administered prior to-, halfway through-, completion of-, and 6 months after chemotherapy completion. Descriptive statistics were used to summarize baseline characteristics. Categorical variables were compared by Chi-square (χ2) test and continuous variables by T-test. The PSQI and FACT scores were analyzed by linear or logistic regression with GEEs. Results: Of the 99 women enrolled, 27 had ovarian, 23 had endometrial, and 49 had breast cancer. 97 were included in the analysis. The breast cohort was younger than their Gyn counterparts: 50 vs. 62, (p < .001), and more likely to identify as Hispanic (p = .012). 56% of women endorsed poor sleep quality at baseline. By mid-treatment, both cohorts reported a significant reduction in sleep quality (p = .008) and QOL (p = .0003) that did not persist at end of- or 6 months post-treatment. Increased need for sleep medications (p = .012) and reduction in sleep efficiency (p = .002) were identified mid-treatment. No significant changes in PSQI or FACT-G were seen by end of treatment. At 6 months post treatment, less Gyn patients reported poor sleep quality when compared to baseline (46 vs 53%) while experiencing a significant improvement in QOL (p = .03). Poor sleep quality was correlated with worse QOL at all time points (p < .001). Conclusions: There is a sparsity of research on sleep disturbances in gynecologic malignancies. In this study, three quarters of all women reported poor sleep quality by mid-treatment with concomitant decrease in QOL. Poor sleep was reported by nearly 50% of women at all other time points. Larger studies need to be done to further define the problem and identify areas suitable for interventions.
Long-term symptom burden and quality of life in metastatic melanoma patients treated with checkpoint inhibitors.
Authors: Mamoor Maha , Lavery Jessica A. , Sidlow Robert , Rogak Lauren J. , Thom Bridgette , Khan Niloufer , Baxi Shrujal S. , Wolchok Jedd D. , Postow Michael A. , Korenstein Deborah
Published: May 2019

e23090

Background: Patients with metastatic melanoma (MMel) who achieve durable long-term responses to checkpoint inhibitors (CI) represent a new type of cancer survivor, but their long-term quality of life (QOL) is poorly described. We measured symptom burden and long-term QOL in MMel patients treated with CIs at Memorial Sloan Kettering Cancer Center (MSK). Methods: Between February and August 2018 we performed a cross-sectional survey of adult patients with MMel treated with CI at MSK beginning at least 12 months prior to this study. Surveys were self-administered online using RedCap. We assessed patient treatment experience and QOL using the PRO-CTCAE bank, EORTC, EQ-5D, and Fatigue Severity Scale. We performed chart abstraction to assess extent of cancer burden, ECOG status, Charlson Comorbidity Index (CCI), concurrent medical conditions, and immune-related adverse events (irAEs) developing during or after treatment. For analysis, we dichotomized age (< 65 vs ≥65) and months from CI initiation (< 25 vs ≥25). Results: We enrolled 107 patients (39% survey response rate); 106 completed surveys. Participants were 57.0% male and 93.5% white, with median age 60.5 years (IQR: 51.1, 67.5 years). 79.4% had a CCI of 0 at start of CI; preexisting autoimmune disorders were rare. Median time since CI initiation was 36.4 months (range: 14.2, 133.9 months). Median length of CI treatment was 7.3 months (IQR: 2.1, 24.3 months); 15 patients were on treatment at the time of survey completion. Among those off treatment at the time of survey completion, median time off treatment was 27.1 months (IQR: 16.7, 40.4 months). The most common irAEs were rash (34.6%), colitis (24.3%), thyroiditis (19.6%), hepatitis (18.7%), and hypophysitis (13.1%). irAEs did not differ by age. Few patients reported symptoms at time of survey, most commonly aching joints (18%), fatigue (14%), aching muscles (13%), and difficulty sleeping (11%). Few (< 12%) had difficulty with physical, role, emotional, cognitive, or social functioning and almost none (1%) reported anxiety, depression or pain on the EQ-5D. QOL was excellent, with a median of 83.3% on the EQ-5D global health score and no differences based on toxicities or time from treatment. Conclusions: Long-term survivors of MMel patients report few burdensome symptoms after CI therapy and have excellent QOL.
Cognitive impairment and treatment effects among gastrointenstinal stromal tumor survivors: Results of a large online survey.
Authors: Ferguson Robert J. , Manculich Jessica , Snitz Beth E. , Bovbjerg Dana H. , Duensing Anette
Published: May 2019

e23092

Background: Cancer-related cognitive impairment (CRCI) is chronic and negatively affects quality of life (QOL) for a large portion of cancer survivors. To date, no studies have exclusively examined CRCI among gastrointestinal stromal tumor (GIST) survivors. Tyrosine kinase inhibitors (TKI), such as imatinib mesylate, have greatly increased median survival of individuals with GIST, so evaluating CRCI for this group is important. We report results of a large online survey of GIST survivors to ascertain prevalence, course and features of CRCI. Methods: A web-based survey utilizing validated patient reported outcomes (PRO’s) and de-identified demographic questions was developed. Respondents answered questions on age, gender, education, medical/cancer history and treatment. Estimated IQ was derived from demographic indexing. The FACT-Cog V3 and PROMIS Short Forms 8a assessed cognitive complaints, fatigue, mood, and anxiety. The survey was distributed through GIST Support International, the GIST Cancer Research Fund, Sarcoma Patients EuroNet and the Life Raft Group. Results: Across 4 continents, 485 adult GIST survivors (median age = 59 years, 71.8% female, 88.7% Caucasian) completed the survey. Respondents were 6.29 (sd = 5.19) years post-diagnosis with 88.0% percent on, or at least having started, imatinib. A majority (63.9%) indicated significant negative QOL impact as assessed by FACT-Cog Perceived Cognitive Impairments scale (PCI). PCI did not correlate with emotional distress or fatigue, as in other cancer samples. Type of surgery, current use/non-use of imatinib or other therapy was not associated with PCI. However, GIST survivors ≥ 5 years post-diagnosis had significantly worse PCI scores than survivors < 5 years post-diagnosis (p < 0.05). No differences between survivors with/without B12 deficiency or anemia were found and PCI did not correlate with cognitive reserve (years of education or IQ). Conclusions: Nearly two-thirds of GIST survivors report significant QOL impact of CRCI. Those with ≥ 5 year survival report worse cognitive symptoms, regardless of being on or off current TKI and cognitive symptoms do not appear associated with emotional distress or fatigue. CRCI among GIST survivors appears long term but further research to objectively determine CRCI magnitude and trajectory is warranted.
Novel smartphone app for daily symptom reporting for active chemotherapy patients.
Authors: Marshall John , Wiebe Lauren Allison , Isenstein Howard
Published: May 2019

e23119

Background: Clinicians, payors and patients are recognizing the value of enhanced symptom monitoring for ambulatory patients between chemotherapy encounters. However, enabling technologies to do so are nascent. Methods: A patient-facing Smartphone app and a clinician-facing dashboard were developed for providers to easily monitor key symptoms in ambulatory patients. Both EHR-integrated and standalone versions were available by provider preference. 250 patients with breast, lung or gastrointestinal cancer in active chemotherapy and their paired clinicians were recruited at three hospital-based practices to test the feasibility and usability of our system. Patients were prompted to report symptoms once per day Monday-Friday. Patients could also track their symptoms and obtain standardized self-care guidance at any time. Clinicians could access their patients’ data via the dashboard at any time. The treating team ould also receive e-mail alerts based on a pre-approved symptom triage protocol. Results: All enrolled clinicians and patients were able to access and use the technology. Clinicians accessed the symptom management dashboard at least once per weekday on average. 75% of clinicians indicated that the technology reduced their workflow somewhat or had no effect on it. The majority (71.5%) of clinicians indicated that the frequency of alerts they received was acceptable. 100% of clinicians who accessed the tool when integrated into the EHR indicated that the it was very convenient to use vs. only 20% of the clinicians who accessed the standalone version. 39.4% of patients reported using our technology on a daily basis. 77.9% of patients said that they would recommend the Smartphone App. Conclusions: The CarePrompter electronic patient-reported outcomes (ePRO) monitoring system demonstrated high technical feasibility and usability, particularly when integrated with the EHR, suggesting that technical barriers to providing robust real-time and historical symptom data are less formidable than they appear.
Cachexia in head and neck squamous cell carcinoma (HNSCC) patients (pts) after cisplatin-based chemoradiation (CRT): A cross-sectional study.
Authors: Castro Gilberto , das Neves Willian , Rivelli Thomás Giollo , Simao Eduardo Furquim , Martins Renata Eiras , Kulcsar Marco Aurelio Vamondes
Published: May 2019

e23138

Background: Cachexia is a wasting syndrome that may affect HNSCC pts, contributing to their dismal prognosis. We aimed to study the frequency of cachexia in HNSCC survivors treated with CRT with curative intent. Methods: Cross-sectional study that included 120 consecutive pts from Jan/2014 to Feb/2017, over 18 y.o. and who were previously treated with definitive or adjuvant CRT for HNSCC (nasopharynx, oropharynx [OP], oral cavity [OC], hypopharynx and larynx [L]). Eligible pts were in regular follow-up for at least 2 years in the multidisciplinary team, with no evidence of disease. Medical history, body weight, height, mid-arm muscle circumference (MAMC) and muscle strength (MS, handgrip dynamometer) were measured, and laboratory tests (hemoglobin [Hb], albumin and C-reactive protein [CRP]) were obtained. Cachexia was diagnosed when there was any weight loss in the previous year, and at least 3 of the following: reduced grip muscle strength, fatigue, anorexia, low lean body mass, or laboratorial alterations (Hb < 12 g/dL, serum albumin < 3.2 g/dL or CRP > 5.0 mg/L). A subjective assessment of nutritional status was made based on the Patient-Generated Subjective Global Assessment (PG-SGA) in its short form. Results: Median age 59 y.o. (21-78), 88 male (73%). Most common primary sites were OP (42%), L (24%) and OC (19%). Median follow-up was 42 mo. (24-125). There was a predominance of locally advanced disease at diagnosis: 73% T3/T4 and 72% N+. The mean weight was 64.5 kg (±14.6) pre-CRT, 57.8 kg (±12.2) post-CRT (p 0.02) and 63 kg (±11.8) in the present evaluation (p NS). Dysphagia was a complaint in 88 pts (73%). Cachexia was diagnosed in 42 pts (35%). As expected, cachectic pts (CP) presented lower MAMC (25.1 vs. 27.2 cm, p 0.0002) and MS (24.3 vs. 29.5 kgf, p 0.004). Higher mean CRP (12.7 vs. 4.2 mg/L, p 0.0001) and lower Hb (13.1 vs.13.9 g/dL, p 0.01) were also seen in CP. The PG-SGA score was higher in CP (7.9 vs. 5.7, p 0.006). Conclusions: Cachexia was frequently diagnosed in HNSCC pts with NED after CRT in a long-term follow-up, without evident weight loss. More effective preventive and therapeutic strategies are warranted. Supported in part by FAPESP grant 2014/00172-9.