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Objective: This study examined (a) whether there are a subgroup of cancer patients experiencing the selected psycho-neurological symptoms as a cluster (depression, cognitive impairment, fatigue, sleep disturbance, and pain); (b) whether demographic and clinical characteristics and pro-inflammatory cytokines (IL-1α, IL-1β, IL-4, IL-6, TNF-alpha) are associated with subgroup membership; and (c) whether the activity of indolamine-2.3 dioxygenase(IDO) is associated with pro-inflammatory cytokine activity and psycho-neurological symptom cluster experience., Methods: This was a prospective cohort study where 149 hematologic patients were recruited from a university hospital and 65 healthy volunteers provided control data. Latent profile analyses were conducted to identify subgroups at two time points: the last day of chemotherapy and 1 week after chemotherapy completion. Influencing factors of subgroup membership were examined by logistic regression., Results: A substantial number of patients (33%, 34% at each time point) experienced the selected psycho-neurological symptoms as a cluster. Older age and elevated IL-1α and IL-6 were associated with experiencing the psycho-neurological symptom cluster. IDO activity was higher in the patients experiencing psycho-neurological symptom cluster; and was positively associated with IL-6. Symptom severity, IL-1α, IL-6, and IDO activity were all significantly higher in cancer patients than in the healthy controls. The findings were preserved across time points., Conclusions: The activation of pro-inflammatory cytokines and their cross-talk with IDO may be a common biological mechanism, underlying a psycho-neurological symptom cluster experience. The novel approaches for symptom assessment and management can be developed by assessing multiple psycho-neurological symptoms as a cluster and by targeting their common biological pathway., Competing Interests: Declaration of Competing Interest There is no conflict of interest for this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Biologics have shown marked success over the past decades in disease areas as cancer, immunology and diabetes. However, elevated costs of innovative biologic medicines have led to an inequity in accessibility across the world. While 85% of the world's population lives in low- and middle- income countries (LMIC), 80% of the sales of monoclonal antibodies are attributed to Western countries, highlighting the pronounced market imbalance., Areas Covered: This perspective paper draws some analogies as well as differences between biosimilars and generics, aims to address the unmet need for treatment with biologics in LMICs by reviewing possible causes, economic and social, of low access, displaying the disparity between LMICs and HIC, and suggets countermeasures for this unmet medical need in LMICs., Expert Opinion: It is up to all stakeholders to capitalize on the opportunity that biosimilars provide, mostly by committing to transparent collaboration, to make biotherapeutics accessible to all, regardless of region or country of residence.

Background: We aimed to estimate the incremental lifetime effects, costs, and net-monetary-benefit (NMB) of knowing BRCA information by testing of patients with low-risk localized prostate cancer (PCa) in the US and guiding subsequent screening and treatment, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1)'with BRCA information' and (2)'without BRCA information.' We also estimated the expected value of perfect information., Methods: The incremental NMB (INMB) quantified the monetized benefit per person of knowing BRCA status. The net-monetized-value of knowing BRCA information was estimated by multiplying the INMB with the eligible population., Results: The INMBs of knowing BRCA information were $43,357 (payer) and $43,487 (society). in payer and societal perspectives, respectively. Escalated to the eligible patients in 2020, knowing BRCA status resulted in net monetized lifetime value of $1.7 billion (payer and society) for the 2020 cohort; and yielded accumulated net-monetized-value of $28.0 billion (payer) and $28.1 billion (society) over 16 yearly cohorts of eligible PCa patients., Conclusions: The economic value of knowing BRCA status for all low-risk localized PCa patients in the US provides short-term and long-term evidence for BRCA testing to screen early and optimize treatment.

This study examined whether (a) cancer patients in two cohorts reported greater subjective cognitive impairment (SCI) in prevalence and severity than noncancer healthy controls; and (b) selected psychoneurological factors (fatigue, stress, and sleep disturbance) contribute to such differences. Data from 60 prechemotherapy cancer patients, 81 active-chemotherapy cancer patients, and 116 noncancer healthy controls were analyzed using hierarchical regressions. The prevalence rate of SCI was higher in the prechemotherapy cancer cohort (41.6%) and in the active-chemotherapy cancer cohort (46.9%) than in healthy controls (21.5%; p  < .001). SCI severity was also higher in two cancer cohorts than noncancer controls ( p  < .001). The two cancer cohorts were similar to each other in severity and prevalence of SCI. The two cancer cohorts experienced higher fatigue, stress, and sleep disturbance than healthy controls. After controlling for psychoneurological factors, however, the two cancer cohorts did not differ from healthy controls in experiencing SCI in prevalence and severity. Psychoneurological factors may be a major determinant of the higher prevalence and severity of SCI in cancer patients.

Objectives: This systematic review of longitudinal studies, assessing subjective cognitive impairment (SCI) reported by adult cancer patients, aimed to summarize evidence on the impact of chemotherapy on SCI, identify moderators of SCI, and evaluate methodological issues., Methods: Data accrued from Pubmed, EMBASE, CINAHL, PsychInfo, and the Cochrane library. Inclusion criteria were original studies, an exclusively adult sample, valid and reliable subjective cognitive measures, and at least one baseline data point prior to and another after the initiation of chemotherapy. Data were collected on the sample composition, data-collection time points, outcome measures, statistical analysis, and major findings (ie, longitudinal changes in prevalence, severity, and associated factors)., Results: Forty articles published between 2004 and 2019 were retained: 21 examined chemotherapy-treated patients only, and 19 employed control groups. Findings were mixed, with slightly more studies supporting the impact of chemotherapy on SCI. SCI tended to be more prevalent and severe after initiating chemotherapy, compared with patients' own baseline and controls not treated with chemotherapy. Impact appeared to be acute and more likely limited to subsamples. Most studies examining non-breast-cancer samples reported the lack or limited impact of chemotherapy on SCI. The most consistent moderators were depression and fatigue. Methodological issues regarding sampling design, measurement, and statistical analysis were discussed., Conclusion: More rigorously designed longitudinal studies would clarify direct and indirect effects of chemotherapy on SCI., (© 2020 John Wiley & Sons, Ltd.)

Aim: This study aimed to report patterns of biosimilar filgrastim prophylaxis and outcomes of chemotherapy-induced neutropenia (CIN)/febrile neutropenia (FN) in patients with hematological malignancies or solid tumors., Patients & Methods: MONITOR-GCSF is a real-world study of 1447 cancer patients receiving CIN/FN prophylaxis with biosimilar filgrastim (solid tumors: 77.2%; hematological malignancies: 22.8%)., Results: Differences in prophylaxis intensity and day of initiation relative to guideline recommendations were observed. In hematology patients, higher rates of CIN and FN occurred at cycle level, and rate of FN was higher at patient level (9.1 vs 5.0% in solid tumor patients)., Conclusion: Adequate GCSF support in hematology and solid tumor patients is important to prevent CIN/FN and related hospitalizations and chemotherapy disturbances.

Aim: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis., Methods: Simulation study using cost data for the USA under consideration of several prophylaxis patterns., Results: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz)., Conclusion: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.

Background: Myelotoxic chemotherapy is associated with chemotherapy-induced (febrile) neutropenia (CIN/FN). The MONITOR-GCSF study evaluated biosimilar filgrastim (Zarzio®) prophylaxis patterns, associated outcomes, and determinants. We performed stratified analyses comparing elderly and non-elderly patients., Methods: Comparative (elderly/non-elderly) analysis of demographics and clinical status, prophylaxis, associated CIN/FN outcomes (CIN grade 4 [CIN4], FN, CIN/FN-related hospitalizations and chemodisturbances, composite), and, per hierarchical modeling, determinants thereof evaluated at the patient- and cycle-level., Results: There were no significant differences between both cohorts in prophylaxis initiation/duration and associated outcomes, but proportionately more elderly patients were correctly-prophylacted and fewer over-prophylacted. Common determinants of poor CIN/FN outcomes included concomitant antibiotic prophylaxis, impaired performance status, and any grade CIN in a previous cycle, whereas common determinants of good outcomes included over-prophylaxis and prophylaxis initiation within 24-72h. In the elderly, female gender, liver/renal/cardiovascular disease, secondary prophylaxis, and under-prophylaxis were associated with poorer outcomes. In the non-elderly, CIN4 at baseline or in a prior cycle was associated with poorer CIN/FN outcomes, and higher biosimilar filgrastim dose and, perhaps counter-intuitively, under-prophylaxis with better outcomes., Conclusion: Adequate GCSF support is essential for all patients, but especially for elderly patients with serious chronic disease, certainly, if concomitant antibiotic prophylaxis is indicated and if a CIN4 episode occurred in a prior cycle. The potential impact of impaired performance status, especially ECOG≥2 at chemotherapy start or a worsening to such during chemotherapy; under-prophylaxis, including inadequate secondary prophylaxis, should be considered in elderly patients. Timely GCSF initiation and over-prophylaxis is associated with lower rates of adverse CIN/FN events in elderly and non-elderly patients, and should be further evaluated in prospective randomized trials., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Data from an ongoing European pharmacoepidemiological study (MONITOR-CKD5) were used to examine congruence between physician-reported risk-based individualisation of target haemoglobin (Hb) and the actual Hb targets set by these physicians for their patients, as well as actual Hb levels in their patients., Methods: Physician investigators participating in the study completed a questionnaire about their anaemia practice patterns and attitudes post-TREAT at the start of the study (T1) and in summer 2013 (T2). These data were compared with the Hb targets identified at baseline for actual patients (n = 1197) enrolled in the study. Risk groups included presence/absence of hypertension, diabetes, cardiovascular complications, history of stroke, history of cancer, and age/activity level (elderly/inactive or young/active)., Results: At each time point, more than three quarters of physicians responded that results from the TREAT study, in patients not on dialysis, have influenced their use of erythropoiesis-stimulating agents in patients on haemodialysis. At T1, there was a clear difference in physician-reported (theoretical) target Hb levels for patients across the different risk groups, but there was no difference in patients' actual Hb levels across the risk groups. A similar disparity was noted at T2., Conclusions: Physicians' theoretical attitudes to anaemia management in patients on haemodialysis appear to have been influenced by the results of the TREAT study, which involved patients not on dialysis. Physicians claim to use risk-based target Hb levels to guide renal anaemia care. However, there is discrepancy between these declared risk-based target Hb levels and actual target Hb levels for patients with variable risk factors.

Aim: We simulated the budget impact of biosimilar erythropoiesis-stimulating agent (ESA) in EU G5 countries., Materials & Methods: Three models were built to estimate the number of patients who could be provided with antineoplastic therapy with rituximab, bevacizumab or trastuzumab from cost savings of biosimilar erythropoietin use in a hypothetical panel of 100,000 patients. The associated number of patients needed to convert to biosimilar ESA to provide such treatments was also calculated., Results: Under fixed dosing, the savings from 100% conversion were €110,592,159, translating into an additional 9770 rituximab, 3912 bevacizumab, or 3713 trastuzumab treatments. Under weight-based dosing, the savings from 100% conversion were €146,170,333, corresponding to an additional 12,913 rituximab, 5171 bevacizumab or 4908 trastuzumab treatments. The number of patients needed to convert ranged from four to 51., Conclusion: Using biosimilar ESA for supportive cancer care yields significant savings and increases accessibility to primary antineoplastic therapy in a budget neutral way.

Introduction: The Anemia Cancer Treatment study assessed hemoglobin (Hb) outcomes following treatment with erythropoiesis-stimulating agents (ESA) in anemic (Hb≤11g/dL) patients in Europe. We replicated the original analyses stratifying by age, namely patients aged ≥70 (n=637) versus those aged<70 (n=1555)., Materials and Methods: A secondary analysis of Hb outcomes was assessed over 8-10weeks. Treatment response criteria included increases of Hb≥1g/dL, Hb≥1g/dL over 8weeks, and Hb≥2g/dL over the course of the study period., Results: Mean Hb increased from similar levels of 9.5g/dL [p=not significant (ns)] at visit one to 10.9g/dL (p=ns) at visit three (both p<0.001). Patients aged≥70 had higher mean Hb at visit two (10.6g/dL vs. 10.3g/dL, p<0.001). Cohorts did not differ in treatment response rates (all p=ns). Mean performance status differed between cohorts at each visit (all p≤0.011); both groups showed significant improvements (both p<0.001). Immediacy of response was a consistent determinant but was more pronounced among patients aged≥70. Less consistent determinants included performance status in the age≥70 group, as well as hematological malignancy and Hb at ESA start in the age<70 group. The proportion of variance in Hb outcomes attributable to treatment center ranged from 0.090 to 0.289 in the age≥70 cohort and 0.126 to 0.361 in the age<70 cohort., Conclusions: Both groups achieved similar Hb levels with the age≥70 cohort showing a higher initial evolution rate and potentially a different Hb response trajectory. Patients age≥70 were more likely to benefit from ESAs if showing an early erythropoietic response and exhibiting no or little impairment in performance status. Differential attribution of variability in older vs. younger adults suggests that individualization of ESA therapy may facilitate Hb response in geriatric patients with cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose of Review: Within a broader perspective on the next challenges in oncologic symptom cluster research, the objectives of this review are to examine the statistical methods that have been used to quantify and/or model the dynamic nature of symptom clustering, the methodological issues associated with those methods, and the statistical modeling techniques for the underlying mechanisms of symptom clustering., Recent Findings: Correlation, factor analysis, principal component analysis, and cluster analysis are analytical methods to identify symptom clusters and/or to examine the influence of symptom clusters on patient outcomes. More recent techniques include latent variable methods, such as latent profile analysis, to examine the phenotypes of symptom cluster experience and growth modeling to examine the longitudinal nature of symptom cluster experience. Future endeavors include an investigation of the underlying mechanisms of symptom clustering using longitudinal data analysis. The methodological issues include the domain of the symptoms, measurement errors, stability of the solution within the data, measurement timing, and sample size., Summary: Each method has unique strengths and weaknesses, and the method choice should be driven by the aims and research questions of a given study.

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of Zarzio(®) in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates statistical methodologies from the social and behavioral sciences; assesses factors predictive of poor treatment response; and evaluates the congruence of treatment with EORTC guidelines and the approved label. This pan-European study will recruit at least 1000 patients from a minimum of 75 centers and follow them for maximum 6 cycles of chemotherapy. Apart from descriptive and associative procedures, statistical analysis will include variance attribution methods; hierarchical linear, logistic, and Poisson modeling; Kaplan-Meier time-to-event analysis, Mantel-Cox log-rank or generalized Wilcoxon-Breslow tests, and Cox proportional hazards modeling; and clustering and related data mining techniques., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The MONITOR-GCSF study is an international, prospective, observational, pharmaco-epidemiological study to evaluate the multi-level factors and outcomes associated with the use of biosimilar filgrastim in the prophylaxis of febrile neutropenia in chemotherapy-treated cancer patients. The background and methodology of this study are described in an article published concurrently in this journal. As important amendments have been made to the protocol, and the purpose of the prior article was to serve as a resource for future referencing, we detail these amendments in this present article: explicit statement about the use of biosimilar filgrastim for both primary and secondary prophylaxis of chemotherapy-induced febrile neutropenia in the objectives and methodology of the study; length of observation; the addition of stage III and stage IV ovarian cancer and multiple myeloma to the tumor types studied; and the deletion of dose dense chemotherapy regimens as an exclusion criterion., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Goal of Work: The goal of this study is to test the validity of RESPOND, a web-based decision support system to assess and manage anemia in cancer patients as per the European Organisation for Research and Treatment of Cancer (EORTC) guidelines. The intraclass correlation metrics for the algorithmic definitions were reported previously. Reported here are the concurrent validity, the extent to which clinicians' anemia management is guidelines-congruent when using the system; and discriminant validity, the extent to which clinicians practice in congruence with guidelines when vs. when not using the system., Patients and Methods: Hybrid matched design with precohort (retrospective; clinicians not using RESPOND) and postcohort (prospective; clinicians using RESPOND) of anemic patients matched on cancer type and chemotherapy regimen and followed up over 4 months after treatment initiation with erythropoietic proteins (34 patients per cohort; total N = 68). Congruence scores quantified the extent to which anemia management was congruent with the EORTC guidelines (range 0-10)., Main Results: Hemoglobin (Hb) increased significantly for both cohorts, but the postcohort group showed more rapid rate of Hb increase over time (p < 0.006), higher Hb by visit 4 (p = 0.007), and greater Hb increase by visit 4 (p = 0.006). Concurrent validity was high with mean postcohort congruence scores of 8.18 +/- 1.38. Discriminant validity was inferred from statistically significant differences in mean congruence scores between cohorts (p < 0.001) and from the postcohort having odds ratios of 3.64 for patients to reach Hb >or= 11 g/dL and 2.91 to achieve Hb >or= 12 g/dL., Conclusions: RESPOND, a validated computerized clinical guidance system with an incremental effect beyond the pharmacotherapeutic effect of erythropoietic proteins, offers clinicians accurate and safe guidance in managing anemia in cancer patients.

Objectives: To examine anaemia management in cancer patients treated with erythropoiesis-stimulating agents (ESAs) in Europe., Methods: Retrospective pharmacoepidemiologic study of 2192 patients from 307 centres. Minimum of 3 visits over 8-10 weeks with ESA treatment initiated at visit 1., Results: Most patients were treated per guidelines, except for low iron supplementation rates. Mean Hb rose from 9.54+/-0.95 g/dl to 10.88+/-1.49 g/dl at visit 3, without concomitant rise in WHO/ECOG score. Response rates were 65.0% (Hb increase (upward arrow) > or = 1 g/dl); 54.3% (Hb increase (upward arrow) > or = 1 g/dl in 8 weeks); 38.9% (haematopoietic response); 33.7% (Hb increase (upward arrow) > or = 2 g/dl) and 18.8% (Hb between 12.0 and 12.9 g/dl), Conclusions: Treatment patterns were guideline congruent, except for (intravenous) iron supplementation. Hb increased by 1.34 g/dl. A net erythropoiesis boost of Hb > or =1 g/dl is attainable in two-thirds of patients and should be condensed to 8 weeks on an individual patient basis. Anaemia management in Europe has improved significantly. The general effectiveness and relative safety of judicious ESA treatment are evident.

Purpose: To model the relationship between scores for practicing in congruence (CSs; 0-10) with EORTC guidelines for erythropoietic proteins (EPs) and haemoglobin (Hb) outcomes observed in the validation study of the RESPOND system., Methods: Thirty four patient pairs matched on cancer type and chemotherapy in pre- (retrospective; clinicians not using RESPOND) and post-cohorts (prospective; clinicians using RESPOND) followed over 4 months following EP treatment initiation. CSs quantify the extent that care was guideline-adherent. Linear and logistic regressions controlling for cohort examined Hb outcomes as a function of CSs., Results: A one-point increase in CS was associated with 0.60g/dL increase in Hb at month 4 (R(2)=0.40) and 0.56g/dL increase in Hb change from month 1-4 (R(2)=0.33). Each one-point increase in CS increased the odds of reaching Hb>or=11g/dL by 3.14 (R(2)=0.42) and Hb>or=12g/dL by 2.77 (R(2)=0.45)., Conclusion: Guideline-adherent EP treatment may improve Hb outcomes but specifically designed outcomes studies are necessary.

This study examined statistical methods to identify and quantify symptom clusters in diverse disciplines, discussed methodological issues in symptom cluster research in oncology, and provided guidance to researchers and clinicians as to the choice and conceptual implications of particular methods. Correlation and related measures of association show the mathematical evidence of a concurrent tendency for 2 or more symptoms. Graphical modeling reveals a more concrete image of possible symptom clusters and provides an idea as to how and why they are correlated. Structural equation modeling can be used to identify symptom clusters with a large number of symptoms, complex relationships, and/or directional relationships. Factor analysis can identify groups of symptoms which are interrelated due to a common underlying cause. Cluster analysis can group symptoms which have similar patterns across patients and find clinical subgroups based on symptom experience. The best strategy to study symptom clusters is to combine various methods while recognizing the strengths and limitations inherent in each method. A tight partnership of clinicians, clinical oncology researchers, and statisticians is essential. Designing a research to identify symptom clusters involves practical issues related to levels of measurement, dimensionality, confounding variables, symptom selection, and heuristic versus deterministic search.

Goal: The benefit of supportive care with erythropoiesis-stimulating agents (ESAs) for patients with cancer-related anaemia is well known. However, the European Cancer Anaemia Survey (ECAS, data from 2001) showed that about 60% of cancer patients with anaemia do not receive any treatment. Since ECAS, evidence-based guidelines have provided recommendations for ESA use, but it is not known to what extent current treatment patterns follow these guidelines. To address this issue, the Anaemia Cancer Treatment (A.C.T.) study was initiated. The background to the development of the A.C.T. study and study methodology are described., Materials and Methods: The A.C.T. study is a global, retrospective, pharmacoepidemiologic study of at least 2,560 medical records of anaemic patients with cancer who were previously treated with an ESA from a minimum of 186 centres. Records from patients aged greater than or equal to 18 years with a diagnosis of solid tumour or myeloma or lymphoma and who were started on ESAs 3-12 months before inclusion and followed for 8-10 weeks will be eligible. Factors associated with ESA non-responsiveness will also be evaluated., Main Results: Completion of the European phase of the study is anticipated in late 2007 with the rest of the world closing in late 2007 or early 2008. Publication of findings is anticipated in 2008., Conclusions: By examining the extent to which anaemia management in clinical practice is congruent with best practice guidelines, the A.C.T. study will provide a further foundation for the development of evidence-based supportive cancer care.

The 2006 EORTC guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. Considering general concerns in medicine about clinicians' adoption of evidence-based guidelines, it is critical to find ways of bringing guidelines to the point of care. We describe the rationale behind RESPOND, a web-based clinical guidance system based on the EORTC guidelines, and the methodologies of two studies conducted to validate the system. In a first descriptive study, experts are asked to rate the accuracy of every algorithm derived from the guidelines. In a second step and using a hybrid matched pre-post design, separate retrospective and prospective patient cohorts matched by type of cancer and similarity of chemotherapy regimen (33 pairs) are used to examine the extent to which clinicians' practice patterns converge with the EORTC guidelines when they use or not use the RESPOND system. It is hypothesized that these studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool.

As part of the development of a computerized clinical decision support system for anemia management in cancer patients, we applied psychometric principles and techniques to assess the accuracy of the algorithmic operationalizations of a set of evidence-based practice guidelines. In an iterative rating process, five medical and nursing experts rated 27 algorithmic sets derived from 18 guidelines, the objective being an intraclass coefficient (ICC) exceeding 0.90. The first round of review yielded an ICC of 1.00 for 22 sets. After revision and resubmission to the expert panel, an ICC of 1.00 was obtained for the additional five sets. The evolving decision support system is based on algorithms that accurately specify evidence-based guidelines for anemia management in cancer patients.