Treatment Outcome Variables Research Articles

Successful Use of Adalimumab for Treating Rheumatoid Arthritis with Autoimmune Sensorineural Hearing Loss: Two Birds with One Stone: Figure 1.

<h3>Background</h3> Despite the availability of evidence-based treatments for posttraumatic stress disorder (PTSD), significant heterogeneity in the effectiveness of PTSD treatment persists, especially in community settings. Client demographics used to understand this variability in treatment outcome and dropout have yielded mixed results. Despite increasing evidence for the importance of attending to treatment engagement in community settings, few studies have explored client-level predictors. <h3>Aim</h3> The purpose of this study is to explore client-level predictors of treatment outcome and dropout beyond client demographics, and to identify client-level predictors of treatment engagement in community settings. <h3>Method</h3> Secondary data analysis was conducted with data collected as part of an implementation-effectiveness hybrid study of cognitive processing therapy (CPT) for PTSD in a diverse community health centre. Providers (n=19) treated (n=52) clients as part of their routine clinical care. Non-demographic client-level predictors included barriers to treatment, quality of life, session-level language and employment history assessed at baseline. Treatment engagement included number of weeks in the study, number of sessions with repeated CPT content, number of unique CPT sessions attended, frequency of session attendance and consistency of session attendance. <h3>Results</h3> Results showed language as a significant predictor of treatment engagement. There were significant differences between Spanish and English-speaking clients, with the former having a tendency to repeat more session content than the latter (β=1.4 sessions, <i>p</i>=0.003), and also less likely to attend treatment frequently (<i>r</i>=0.62, <i>p</i>=0.009) and consistently (<i>r</i><i>=</i>0.57, <i>p</i>=0.027) if high logistical and financial barriers were endorsed. Irrespective of language, clients who reported high quality of life at baseline were less likely to repeat CPT session content (β=−0.3, <i>p</i>=0.04), and those with increased baseline barriers to treatment had deceleration in PTSD symptom improvement over time (β=−0.62, <i>p</i>&lt;0.05). In terms of treatment engagement moderators impacting treatment outcome, clients who repeated more session content were more likely to complete treatment (OR=1.84, <i>p</i>=0.037). <h3>Conclusion</h3> Identification of client-level predictors of treatment engagement, outcome and dropout is essential to optimise treatment, particularly in community settings.

Physician Characteristics and Variation in Treatment Outcomes: Are Better Qualified and Experienced Physicians More Successful in Treating Patients With Chronic Pain With Acupuncture?

The aim of this paper was to quantify the influence of the physician's training and experience in the field of acupuncture on the outcome in patients with chronic pain. Patients visiting their physician because of chronic low back pain, headache, pain due to osteoarthritis of the knee or hip, or neck pain, were included in 4 multicenter, randomized, controlled studies. All patients received routine care; patients in the acupuncture groups received additional acupuncture treatment (on average 10 sessions). The data was pooled, and the 3-month change from baseline of the SF-36 bodily pain subscale as the main outcome defined. A total of 9,990 patients (mean age 49.6 +/- 13.6 years, 68% female) treated by 2,781 physicians (mean age 46.3 +/- 7 years, 37% female) were analyzed. The physicians had 7.3 +/- 5.2 (mean +/- sd) years of experience in acupuncture and their mean duration of formal acupuncture training had been 287 +/- 321 hours. The outcome was markedly improved in the acupuncture group. We identified only 1 physician characteristic with a significant influence on the outcome: Internists performed better (odds ratio OR = 1.49, confidence interval CI: 1.01;2.18; P = .043); orthopedists worse (OR = .79, CI: .62;1; P = .043) than the average physician. Neither the duration of training nor the duration of experience had any impact on the extent of the acupuncture effect. In this analysis, physician characteristics such as training did not influence patients' outcome after acupuncture, suggesting that formal training parameters have only a limited influence on treatment effect. Other skills such as the therapeutic relationship, which are difficult to measure, may probably play a more important role and should be taken into consideration.

Effect of Adverse Events on Low Back Surgery Outcome

This study was based on a post hoc analysis of data collected from a prospective FDA-regulated trial comparing total disc replacement to fusion surgery. he purpose of this study was to determine if the occurrence of adverse events (AEs) had an impact on outcomes of low back surgery. AEs are rigorously recorded during clinical trials primarily to evaluate the safety of the investigational device. AEs include a wide variety of events including those that are not typically thought of as complications related to the treatment intervention. During the course of a study, many physical events may happen to a patient including injuries from motor vehicle accidents, falling, various joint injuries, cancer onset, gastrointestinal problems, etc. Although these are generally thought of as having nothing to do with the patient's spine surgery, the potential detrimental impact of these AEs on the patient's overall well being may negatively effect responses to outcome assessments used to evaluated the clinical outcome of the spine surgery. Data were collected from an FDA-regulated prospective randomized clinical trial comparing lumbar fusion to total disc replacement. AE and clinical data were analyzed for 155 patients who had reached 24-month follow-up. The number of active AEs, along with event severity (mild, moderate, or severe), and its relationship to surgery (unrelated, possibly related, or causative) were recorded. Clinical outcome was based on VAS, Oswestry, and overall satisfaction at 24-month follow-up. Data were analyzed using ANOVA. There were significant relationships between the presence of active AEs and improvement on VAS pain scores, Oswestry scores, and patient satisfaction (P < 0.05; ANOVA with post hoc Tukey) at 24-month follow-up. Patients with no active adverse events had more than 70% improvement on their VAS and Oswestry scores. Significantly less improvements was seen in the VAS and Oswestry scores for patients with 2 or more active AEs, moderate or severe AEs, and AEs classified as related to the study intervention. Patients with AEs classified as being related to the study intervention were significantly less satisfied than those with no AEs or AEs classified as unrelated to the surgery. This study was the first to investigate the impact of active AEs on clinical outcome of spinal surgery. While AEs are recorded to evaluate the safety of new treatments, this study found that AEs also play a role in explaining some of the variation in treatment outcome.

Glycomics: Relevance for Personalized Medicine

Glycomics is an emerging field of research that examines the structure and function of glycans attached to biomolecules. Glycans are chains of sugars that often form complex branched structures on proteins or lipids. Study of glycans represents a previously “untapped” and overlooked field of inquiry in personalized medicine. In the past, technological approaches in personalized medicine heavily relied on high-throughput genotyping or gene expression analyses with relatively little exploration of the downstream biological processes such as glycans and associated variability among individuals and populations. Glycans are important modulators of numerous biological processes that determine person-to-person differences in susceptibility to common complex diseases and response to drug treatment. The heterogeneity and diversity of glycans in part reflect the genetic, population ancestry and age of each patient, as well as stages of disease and nutritional/environmental exposures. However, little effort has been made thus far to exploit the glycosylation state of a patient in relation to prevention of future disease risks or to determine the appropriate treatment for an individual patient. On the other hand, the vast heterogeneity and complexity of glycans limit their comprehensive study. Recent developments in glycan arrays now offer new possibilities in the horizon to achieve a high-throughput profiling of glycan diversity to discover novel molecular targets that are druggable, and better understand and predict variability in drug treatment outcomes. Glycan arrays present carbohydrate ligands in a manner that physiologically mimics interactions at cell-to-cell interfaces through multivalent binding. Glycomics can significantly complement the genomics and proteomics tools that are already being evaluated for developing personalized medicines. This paper aims to give an overview of the current status of glycan research and applications in diagnostic medicine. Moreover, we propose that glycomics and nanobiotechnology form a powerful and synergistic technological combination on the critical path to personalized medicine. Keywords: Glycan arrays, glycomics, nanobiotechnology, personalized medicine, theragnostics

Response to Treatment with Placebo, Medication or Psychotherapy in Severe Non- Psychotic Major Depressive Disorder

Severe major depressive disorder (MDD) is associated with poorer response to treatment than milder forms of depression, but there is a lack of consensus about the optimal treatment approach. We conducted a qualitative review of the literature for clinical trials of severe MDD in adults (1975 - December 2008), to assess the effects of five treatment approaches: placebo, medication, psychotherapy, combined treatment, and medication augmentation. We found significant variability in treatment outcomes across studies of severe MDD, deriving largely from differences in study design and variability in study samples identified as “severely” depressed. Severely ill patients respond more poorly to placebo and psychotherapy than mildly or moderately depressed patients. Medication monotherapy is superior to psychotherapy alone in the treatment of severe MDD. Combination treatment with medication and psychotherapy shows greater utility in severe, rather than mild or moderate, MDD. Lithium is the best established augmenting agent for severe MDD, particularly in combination with a tricyclic antidepressant. This review indicates the best initial clinical approach to treating severe major depressive disorder is through a combination of medication monotherapy and structured psychotherapy. Future trials in severely ill patients should more fully characterize the clinical and biological aspects of the enrolled patients.

Time limited psychodynamic group therapy

We explore predictors of participation in additional treatment within one year after termination of 39 sessions of psychodynamic group therapy (n=130). The sample was biased due to a 33% dropout at the one-year follow-up of symptomatic less improved treatment completers (N=194). Outcome predictors were the Symptom Check List 90 Revised (SCL-90-R), Millon Clinical Multiaxial Inventory II (MCMI-II), non-symptomatic Psychodynamic Focus, retrospective outcome evaluations, and socio-demographic and psychiatric variables.At follow-up, 57.6% of the patients had been seeking additional treatment for psychological or psychiatric problems; the percentage was 41.6%, when further treatment was defined as participating in more than 5 sessions. The majority (94.8%) was treated within the public health services.Participation in additional treatment was predicted by improvement on the MCMI Antisocial personality disorder scale and a higher SCL-90-R Somatization end-state score. When additional treatment was defined as receiving more than 5 sessions, lack of paid work before treatment (odds ratio 8.0), lack of social network support (odds ratio 2.9), and the Antisocial pre- post difference score (odds ratio 1.6) were significant predictors explaining a total of 26.4% variance. Neither SCL-90-R Global Severity Index (GSI) reliable and clinically significant improvement, therapist recommendations of further therapy, nor socio-demographic, psychiatric and treatment outcome variables were significantly associated with seeking additional treatment.Even though we identified only a small number of predictors for participation in further treatment, our study nevertheless points to the importance of employing reliable and validated methods in the evaluation of treatment outcome and further treatment planning.

The Relations among Measurements of Informant Discrepancies within a Multisite Trial of Treatments for Childhood Social Phobia

Discrepancies between informants' reports of children's behavior are robustly observed in clinical child research and have important implications for interpreting the outcomes of controlled treatment trials. However, little is known about the basic psychometric properties of these discrepancies. This study examined the relation between parent-child reporting discrepancies on measures of child social phobia symptoms, administered before and after treatment for social phobia. Participants included a clinic sample of 81 children (7-16 years old [M = 11.75, SD = 2.57]; 39 girls, 42 boys) and their parents receiving treatment as part of a multisite controlled trial. Pretreatment parent-child reporting discrepancies predicted parent-child discrepancies at posttreatment, and these relations were not better accounted for by the severity of the child's pretreatment primary diagnosis. Further, treatment responder status moderated this relation: Significant relations were identified for treatment non-responders and not for treatment responders. Overall, findings suggest that informant discrepancies can be reliably employed to measure individual differences over the course of controlled treatment trials. These data provide additional empirical support for recent work suggesting that informant discrepancies can meaningfully inform understanding of treatment response as well as variability in treatment outcomes.

Reproducibility of Lung and Lobar Volume Measurements Using Computed Tomography

Lung and lobar volume measurements from computed tomographic (CT) imaging are being used in clinical trials to assess new minimally invasive emphysema treatments aiming to reduce lung volumes. Establishing the reproducibility of lung volume measurements is important if they are to be accepted as treatment planning and outcome variables. The aims of this study were to (1) investigate the correlation between lung volumes assessed on CT imaging and on pulmonary function testing (PFT), (2) compare the two methods' reproducibility, and (3) assess the reproducibility of CT lobar volumes. CT imaging and body plethysmography were performed at baseline and after a 9-month interval in multicenter emphysema treatment trials. Lung volumes were measured at total lung capacity (TLC) and at residual volume (RV). Lobar volumes were measured on CT imaging using a semiautomated technique. The correlations between CT and PFT volumes were computed for 486 subjects at baseline. Reproducibility was assessed in terms of the intraclass correlation coefficient (ICC) for 126 subjects from the control group at TLC and 120 subjects at RV. Correlations between CT and PFT lung volumes were 0.86 at TLC and 0.67 at RV. At TLC, the ICCs were 0.943 for CT imaging and 0.814 for PFT. At RV, the ICCs were 0.886 for CT imaging and 0.683 for PFT. CT lobar volumes showed good reproducibility (all P values < .05). CT lung and lobar volume measurements could be captured in a multicenter trial setting with high reproducibility and were highly correlated with those obtained on PFT. CT imaging showed significantly better reproducibility than PFT between interval lung volume measurements, offering the potential for designing emphysema treatment trials involving fewer subjects.

Lung cancer in women: the differences in epidemiology, biology and treatment outcomes

Although the prevalence of lung cancer in men has been decreasing, it has been increasing in women. Without a doubt, lung cancer is a major health problem for women in the USA, not only owing to its high incidence rate but, more alarming, the high mortality rate. Lung cancer kills more women each year than breast, ovarian and uterine cancers combined. One of the most important risk factors for the development of lung cancer in both men and women is cigarette smoking. Unfortunately, the prevalence of smoking among women has increased significantly since 1980, which is a major concern as epidemiologic data suggest that women may be more susceptible to developing lung cancer than men. Many will argue, however, that after adjusting for tobacco exposure, some studies have failed to show that women are at a higher risk for developing lung cancer. Indeed, the increased risk of lung cancer in women remains controversial. There is, however, little controversy to the fact that the biology of lung cancer differs between the sexes. This paper summarizes the explanations for the sex differences in lung cancer, including differences in molecular abnormalities, growth factor receptors, hormonal influences, differences in cytochrome P-450 enzymes and DNA repair capacity, as well as variations in treatment outcomes.

PP86 Sister chromatid exchanges as marker of genomic instability in familial breast cancer patients

The mechanisms by which antidepressants have their effects are not clear and the reasons for variability in treatment outcomes are also unknown. However, there is evidence from candidate gene research that indicates gene expression changes may be involved in antidepressant action. In this study, we examined antidepressant-induced alterations in gene expression on a transcriptome-wide scale, exploring associations with treatment response. Blood samples were taken from a subset of depressed patients from the GENDEP study (n=136) before and after eight weeks of treatment with either escitalopram or nortriptyline. Transcriptomic data were obtained from these samples using Illumina HumanHT-12 v4 Expression BeadChip microarrays. When analysing individual genes, we observed that changes in the expression of two genes (MMP28 and KXD1) were associated with better response to nortriptyline. Considering connectivity between genes, we identified modules of genes that were highly coexpressed. In the whole sample, changes in one of the ten identified coexpression modules showed significant correlation with treatment response (cor=0.27, p=0.0029). Using transcriptomic approaches, we have identified gene expression correlates of the therapeutic effects of antidepressants, highlighting possible molecular pathways involved in efficacious antidepressant treatment.

Gender differences in client–provider relationship as active ingredient in substance abuse treatment

The client–provider relationship is increasingly evaluated as an active ingredient in the delivery of substance abuse treatment services. This study examines gender differences in client–provider relationship as an important treatment ingredient affecting retention in treatment and reduced post-treatment substance use. The study uses data collected for the National Treatment Improvement Evaluation Study (NTIES), a prospective, cohort study of U.S. substance abuse treatment programs and their clients. Data on individual characteristics were collected at the pre-treatment interview; on client–provider relationship and services received at treatment exit; and on post-treatment drug use at 12 months post-treatment. The analytic sample consists of 3027 clients from 59 service delivery units (1922 men and 1105 women). Structural equation modeling (SEM) was used to assess the structural relations and causal connections between relationship and service variables and treatment outcome variables. Results indicate that a positive client–provider relationship is related directly to longer duration and reduced post-treatment drug use for the total sample and for men analyzed separately. For women, a positive client–provider relationship was related directly to treatment duration and only indirectly to reduced post-treatment drug use. The findings point to the significance of including client–provider relationship in service delivery models – both as a therapeutic element as well as an element facilitative of matching services to specific client needs.

Mindfulness-based stress reduction for chronic pain conditions: Variation in treatment outcomes and role of home meditation practice

Objective This study compared changes in bodily pain, health-related quality of life (HRQoL), and psychological symptoms during an 8-week mindfulness-based stress reduction (MBSR) program among groups of participants with different chronic pain conditions. Methods From 1997-2003, a longitudinal investigation of chronic pain patients ( n=133) was nested within a larger prospective cohort study of heterogeneous patients participating in MBSR at a university-based Integrative Medicine center. Measures included the Short-Form 36 Health Survey and Symptom Checklist-90-Revised. Paired t tests were used to compare pre–post changes on outcome measures. Differences in treatment effect sizes were compared as a function of chronic pain condition. Correlations were examined between outcome parameters and home meditation practice. Results Outcomes differed in significance and magnitude across common chronic pain conditions. Diagnostic subgroups of patients with arthritis, back/neck pain, or two or more comorbid pain conditions demonstrated a significant change in pain intensity and functional limitations due to pain following MBSR. Participants with arthritis showed the largest treatment effects for HRQoL and psychological distress. Patients with chronic headache/migraine experienced the smallest improvement in pain and HRQoL. Patients with fibromyalgia had the smallest improvement in psychological distress. Greater home meditation practice was associated with improvement on several outcome measures, including overall psychological distress, somatization symptoms, and self-rated health, but not pain and other quality of life scales. Conclusion MBSR treatment effects on pain, HRQoL and psychological well-being vary as a function of chronic pain condition and compliance with home meditation practice.

Clinicians' defences: An empirical study

Clinicians' defence mechanisms are strategies used to manage the stress and the negative affects emerging during a therapy session. The first objective of the study is to adapt the defence mechanisms rating scales (DMRS), originally created by Perry for assessing patient defences, in order to evaluate clinician defences. The second objective is to explore the type of defence mechanisms used by clinicians in oncology. The third objective is to study the sensitivity of the instrument by assessing changes in defensive functioning after specific communication skills training (CST) in oncology. Participants (N=20) were oncology clinicians participating in oncology CST. The defence mechanism rating scales for clinicians (DMRS-C) was used to assess the use of the clinicians' defences before and after CST. The instrument showed promising preliminary psychometric properties. Numerous and very varied defences were coded in each session and corresponding to a great variety of defences. After CST, the clinicians' overall defensive functioning (ODF) increased. Considering the defences' levels, a decrease in the use of immature defences was observed. Taking into consideration the importance of clinicians' variables in treatment outcome, this instrument constitutes a promising way of assessing the clinician's strategies used to face the emotional difficulties emerging during the therapeutic encounter.

European Audit on Colorectal Cancer Treatment Outcome – The Next Step in Quality Assurance Initiated by the European Society of Surgical Oncology

In recent years there have been significant improvements in rectal cancer outcome. New surgical techniques and effective neoadjuvant treatment regimens have contributed to these improvements. It is important to spread these advances to every rectal cancer patient and to make sure that it is not only patients treated within the framework of clinical trials who may benefit from these advances. Throughout Europe there have been interesting quality programmes that have been proved to facilitate the spread of up-to-date knowledge and skills among medical professionals, resulting in improved treatment outcomes. Despite these laudable efforts, there is still wide variation in treatment outcomes between countries, regions and institutions, which calls for a European audit on cancer treatment outcomes.

Nationwide outcome registrations to improve quality of care in rectal surgery. An initiative of the European society of surgical oncology

In recent years there have been significant improvements in rectal cancer treatment. New surgical techniques as well as effective neoadjuvant treatment regimens have contributed to these improvements. Key is to spread these advances towards every rectal cancer patient and to ensure that not only patients who are treated within the framework of clinical trials may benefit from these advancements. Throughout Europe there have been interesting quality programmes that have proved to facilitate the spread of up to date knowledge and skills among medical professionals resulting in improved treatment outcome. Despite these laudable efforts there is still a wide variation in treatment outcome between countries, regions and institutions, which calls for a European audit on cancer treatment outcome.

Comparison of the Management of Anemia in Patients with Solid Versus Hematological Malignancies Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated in solid and hematological malignancies. Variability in treatment patterns, outcomes, and response rates in these tumor categories needs to be further explored.OBJECTIVE. To examine differences in anemia treatment patterns, outcomes, and response rates between patients with solid vs. hematological malignancies.DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with 3 time points at approximately 1 month intervals; start of ESA treatment at visit 1. 307 centers in 13 European countries contributed 2192 pts (n=630 with hematological tumors; n=1562 with solid tumors) who were anemic (hemoglobin [Hb] 11g/dL) and treated with an ESA.MEASUREMENTS. Retrospective chart review. Variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise≥1g/dl within 8 weeks, hematopoietic response (Hb rise≥2g/dl or Hb≥12g/dl achieved), Hb rise≥2g/dl, and Hb target range of 12.0–12.9g/dl achieved by visit 3.RESULTS. Pts ranged in age from 18 to 94 years (61.5 12.7) with no difference between groups (p=ns). 95.2% of pts were on chemotherapy, of which 92.9% on standard vs. 7.1% on high dose (solid 94.3% and 5.7% vs. hemato 89.1% and 10.9%, p=0.001); and 40.5% on platinum vs. 59.5% on nonplatinum (solid 49.1% and 50.9% vs. hemato 12.8% and 87.2%, p=<0.001). Types of ESA included epoetin alfa (solid 23.2% vs. hemato 14.4%), epoetin beta (solid 41.7% vs. hemato 44.8%), darbepoetin alfa epoetin alfa (solid 34.6% vs. hemato 40.8%), and other epoetin alfa (solid 0.4% vs. hemato 0.0%; overall differences p<0.001).Table 1.Visit1Visit2Visit3pppSolidHematopSolidHematopSolidHematop(tumor type)(visit)(tumor type X visit)Mean (SD) ESA dose (IU/wk)32601 (10037)31067 (7247)<0.00133455 (11011)32354 (9418)0.03433680 (11757)32309 (9638)0.0270.023<0.001n.s.Median ESAdose (IU/wk)3000030000NA3000030000NA3000030000NANANANAMean (SD) Hb (g/dl)9.6 (0.9)9.3 (1.0)<0.00110.4 (1.2)10.2 (1.5)0.03310.9 (1.4)10.9 (1.7)n.s.0.002<0.001<0.001WHO/ECOG performance status0.89 (0.73)1.11 (0.87)<0.0010.77 (0.71)0.92 (0.71)0.0020.76 (0.75)0.88 (0.76)0.013<0.001<0.0010.004% pts on iron32.3%16.5%<0.00122.6%16.2%0.00622.4%13.7%<0.001<0.001n.s.NA% pts on iron who are on IV iron16.9%24.5%n.s.27.2%34.5%n.s.24.9%32.7%n.s.n.s.n.s.NA% pts with ESA dose escalation5.2%6.5%n.s.3.2%2.5%n.s.n.s.n.s.NATable 2.Hb ↑≥1g/dLHb ↑ ≥1g/dLwithin 8 wksHematopoieticresponseHb ↑≥2g/dLHb target12–12.9g/dLSolidHematoSolidHematoSolidHematoSolidHematoSolidHemato% of pts63.0%70.0%53.4%64.4%35.5%47.5%29.8%43.3%17.9%21.1%p0.002<0.001<0.001<0.001n.s.CONCLUSIONS. Slight increase in mean ESA dose between tumor types and across visits was not in accordance with the stable median ESA dose. Hb increased from visit 1 from visit 3 for all pts, but more so for pts with hematological malignancy, who moreover started out at lower Hb levels. Performance status increased in parallel with Hb, but more so for hematological patients. Hb levels were found to be an interaction of tumor type and time. A concomitant pattern was observed for performance status. Iron supplementation with esp. IV iron was consistently low, however with more hematological pts receiving esp. IV iron. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. Response rates for pts with hematological malignancies were consistently higher than those for solid tumors, except for reaching Hb target of 12–12.9 g/dl. Hematological pts tended to have ESA Rx initiated at lower Hb levels thus showing more room for Hb improvement and therefore greater likelihood to fall in various responder categories. Overall, an increase of 1g/dl is achievable for the majority of pts. Adding time constraints, increasing the threshold level to ≥2g/dl, and/or setting an evidence-based target range of 12–12.9g/dl is associated with lower response rates in both groups, with slight advantage for hematological patients within caution above. ESAs are effective and safe in the management of cancer-related anemia for pts with hematological malignancies and solid tumors.

Management of Anemia in Patients with Hematological Malignancies Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for hematological malignancies. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated.OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with hematological malignancies.DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 152 centers in 13 European countries contributed 630 pts with hematological malignancies who were anemic (hemoglobin [Hb] ≤11g/dL) and treated with an ESA (14.8% of total European sample).MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb ≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3.RESULTS. Pts ranged in age from 18 to 92 years (62.4±15.3). 94.4% of pts were on chemotherapy, of which 89.1% on standard vs. 10.9% on high dose; and 12.8% on platinum vs. 87.2% on nonplatinum. Types of ESA prescribed included epoetin alfa (14.4%), epoetin beta (44.8%), darbepoetin alfa (40.8%). Results are summarized in Table 1.No severe adverse events were reported.Table 1Treatment Patterns & OutcomesVisit 1Visit 2Visit 3PMean (SD) ESA dose (IU/wk)31067 (7247)32354 (9418)32309 (9638)0.001Median ESA dose (IU/wk)300003000030000n.s.Mean (SD) Hb (g/dL)9.3 (1.0)10.2 (1.5)10.9 (1.7)<0.001WHO/ECOG performance status1.11 (0.84)0.92 (0.71)0.88 (0.76)<0.001% pts on iron16.5%16.2%13.7%n.s.% pts on iron who are on IV iron24.5%34.5%32.7%n.s.% pts with ESA dose escalation6.5%2.5%0.028Response RatesHb↑≥1g/dLHb↑≥1g/dL within 8 wksHematopoietic responseHb↑≥2g/dLHb 12-12.9 g/dL70%64.4%47.5%43.3%21.1%CONCLUSIONS. The slight increase in ESA dose was not in accordance with the stable median ESA dose across the three visits. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of 1g/dL over the course of treatment is an attainable goal in over two-thirds of pts with hematological malignancies who are anemic. Adding time constraints, increasing the threshold level to 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In pts with hematological malignancies, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.

Management of Anemia in Lymphoma Patients Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for lymphoma. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated.OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with lymphoma.DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 128 centers in 13 European countries contributed 324 multiple myeloma pts who were anemic (hemoglobin [Hb] 11g/dL) and treated with an ESA (14.8% of total European sample).MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3.RESULTS. Pts ranged in age from 18 to 92 years (58.4±17.6). 96.1% of pts were on chemotherapy, of which 83.4% on standard vs. 16.6% on high dose; and 17.8% on platinum vs. 82.2% on nonplatinum. Types of ESA prescribed included epoetin alfa (13.0%), epoetin beta (43.5%), darbepoetin alfa (43.5%). Results are summarized in Table 1. No severe adverse events were reported.Table 1Treatment patterns and outcomesVisit 1Visit 2Visit 3PMean (SD) ESA dose (IU/week)31851 (6912)33844 (10296)33610 (10199)0.002Median ESA dose (IU/week)300003000030000n.s.Mean (SD) Hb (g/dL)9.3 (1.0)10.2 (1.4)10.9 (1.7)<0.001WHO/ECOG performance status1.04 (0.83)0.98 (0.75)0.90 (0.79)0.002% pts on iron19.2%18.1%15.2%n.s.% pts on iron who are on IV iron16.4%23.3%20.0%n.s.% pts with ESA dose escalation8.4%2.5%n.s.Response ratesHb↑≥1g/dLHb↑≥1g/dL within 8wksHematopoietic responseHb↑≥2g/dL12–12.9g/dL% pts67.9%60.8%44.4%39.8%20.7%CONCLUSIONS. The slight increase in ESA dose was not in accordance with the stable median ESA dose across the three visits. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of 1g/dL over the course of treatment is an attainable goal in two-thirds of lymphoma pts with anemia. Adding time constraints, increasing the threshold level to 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In lymphoma pts, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.

Management of Anemia in Multiple Myeloma Patients Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study

BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated for multiple myeloma. Variability in treatment patterns, outcomes, and response rates in daily clinical practice need to be further investigated.OBJECTIVE. To examine anemia treatment patterns, outcomes, and response rates in the subsample of A.C.T. patients with multiple myeloma.DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with at least 3 time points at approximately 1 month intervals, with visit 1 coinciding with start of ESA treatment. 111 centers in 10 European countries contributed 306 multiple myeloma pts who were anemic (hemoglobin [Hb] ≤11g/dL) and treated with an ESA (14.0% of total European sample).MEASUREMENTS. All data collected through retrospective chart review. Key variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise ≥1g/dL, Hb rise ≥1g/dL within 8 weeks, hematopoietic response (Hb rise ≥2g/dL or Hb≥12g/dL achieved), Hb rise ≥2g/dL, and Hb target range of 12.0–12.9g/dL achieved by visit 3.RESULTS. Pts ranged in age from 26 to 91 years (66.6 11.0). 92.5% of pts were on chemotherapy, of which 94.6% on standard vs. 5.4% on high dose; and 6.7% on platinum vs. 93.3% on nonplatinum. Types of ESA prescribed included epoetin alfa (16.0%), epoetin beta (46.1%), darbepoetin alfa (37.9%). Results are summarized in Table 1. No severe adverse events were reported.Table 1.Treatment patterns & outcomesVisit 1Visit 2Visit 3pMean (SD) ESA dose (IU/wk)30237 (7509)30676 (8012)30760 (8698)n.s.Median ESA dose (IU/wk)300003000030000n.s.Mean (SD) Hb (g/dl)9.2 (1.0)10.3 (1.5)11.0 (1.7)<0.001WHO/ECOG (SD) performance status1.17 (0.84)0.87 (0.66)0.86 (0.73)<0.001% pts on iron13.7%9.2%7.8%n.s.% pts on iron who are on IV iron36.6%46.4%45.8%n.s.% pts with ESA dose escalation4.4%2.5%n.s.Response RatesHb↑≥ 1g/dlHb↑≥1g/dl within 8wksHematopoietic responseHb↑≥ 2g/dl12– 12.9g/dl% pts72.2%68.5%50.7%47.1%21.6%CONCLUSIONS. Mean and median dose did not change over time. Hb increased from visit 1 from visit 3 with a concomitant rise in performance status. Iron supplementation with, in particular, IV iron was consistently low. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. An increase in Hb of ≥1g/dL over the course of treatment is an attainable goal in almost three-quarters of multiple myeloma pts with anemia. Adding time constraints, increasing the threshold level to ≥ 2g/dL, and/or setting an evidence-based target range of 12–12.9g/dL is associated with lower response rates. In multiple myeloma pts, the therapeutic Hb goal to be achieved may need to be determined under consideration of multiple factors, however the general effectiveness of ESAs in this population is evident.

Pharmacogenetics in Colorectal Cancer: a Systematic Review

Pharmacological treatment of colorectal cancer has improved survival rates in recent years. Individual genetic variation in genes associated with metabolism and targets of commonly used drugs can be responsible for variability in treatment outcome and toxicity. Diverse study designs have been used and heterogeneous end points evaluated by studies assessing the association of genetic markers with treatment outcome. We conducted this systematic review, including 51 studies, to present a comprehensive overview and draw further conclusions. To facilitate comparison of reported study results, risk estimates for observed genetic variants in 33 key genes are presented using defined reference categories and recalculated risk estimates based on data provided in original publications, where necessary. Overall, evidence indicates associations of the UGT1A1(*) 28 variant genotype with toxicity after irinotecan treatment, mutations in GSTP1-105 with improved treatment outcome and the XPD-751 variant genotype with poor treatment outcome after oxaliplatin treatment, and amplification of the EGFR gene with improved treatment outcome after therapy with monoclonal antibodies. Adequately powered prospective investigations designed specifically for pharmacogenetics are needed.