European Organisation For Research And Treatment Of Cancer Guidelines Research Articles

Translation and validation of the revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) for evaluating the effectiveness of acute pain services in the Indian population.

Translation and validation of the revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) for evaluating the effectiveness of acute pain services in the Indian population.

Development of a quality of life questionnaire for patients with pancreatic neuroendocrine tumours (the PANNET module).

Pancreatic neuroendocrine tumours (panNET) are heterogeneous neoplasms usually characterised by slow growth and secretion of hormones, which often cause symptoms. The effect of these symptoms on quality of life (QoL) has not previously been examined in detail. EORTC (European Organisation for Research and Treatment of Cancer) guidelines were followed in phases 1–3 to produce a potential module of questions usable for trials in panNET, focusing on three common types of panNET. For two less common types, a list of symptoms was constructed. Following an extensive literature search and phase 1a interviews with patients and healthcare workers, a long list of potential issues (169) was obtained. This list was shown to 12 patients from three countries in phase 1b interviews to check that no items were missed. The list was reduced to 57 issues. The list of issues was converted to questions, mainly from existing validated questions within the EORTC item library. The list of questions was then used in a phase 3 international study in eight countries using seven languages. A provisional module of 24 items is presented for use in nonfunctioning panNET, gastrinoma and insulinoma. This module increases knowledge concerning QoL in this condition and may be a useful adjunct in clinical trials. A phase 4 trial is being considered for validation of this questionnaire.

Assessment of the quality of end-of-life care: translation and validation of the German version of the \u201cCare of the Dying Evaluation\u201d (CODE-GER) - a questionnaire for bereaved relatives

BackgroundInternational studies indicate deficits in end-of-life care that can lead to distress for patients and their next-of-kin.The aim of the study was to translate and validate the “Care of the Dying Evaluation” (CODE) into German (CODE-GER).MethodsTranslation according to EORTC (European Organisation for Research and Treatment of Cancer) guidelines was followed by data collection to evaluate psychometric properties of CODE-GER. Participants were next-of-kin of patients who had died an expected death in two hospitals. They were invited to participate at least eight, but not later than 16 weeks after the patient’s death. To calculate construct validity, the Palliative care Outcome Scale (POS) was assessed. Difficulty and perceived strain of answering the questionnaire were assessed by a numeric scale (0–10).ResultsOut of 1137 next-of-kin eligible, 317 completed the questionnaire (response rate: 27.9%). Data from 237 main sample participants, 38 interraters and 55 next-of-kin who participated for repeated measurement were analysed. Overall internal consistency, α = 0.86, interrater reliability, ICC (1) = 0.79, and retest-reliability, ICC (1, 2) = 0.85, were good. Convergent validity between POS and CODE-GER, r = −.46, was satisfactory. A principal component analysis with varimax rotation showed a 7-factor solution. Difficulty, M = 2.2; SD ± 2.4, and perceived strain, M = 4.1; SD ± 3.0, of completing the questionnaire were rather low.ConclusionThe results from the present study confirm CODE-GER as a reliable and valid instrument to assess the quality of care of the dying person. More over our study adds value to the original questionnaire by proposing a deepened analysis of obtained data. The development of seven subscales increases its potential for further surveys and research.Trial registrationThis study was registered retrospectively on the 25th of January 2018 at the German Clinical Trials Register (DRKS00013916).

Design and development of a disease-specific quality of life tool for patients with aplastic anaemia and/or paroxysmal nocturnal haemoglobinuria (QLQ-AA/PNH)\u2014a report on phase III

To date, instruments to measure quality of life (QoL) specifically for patients with acquired aplastic anaemia (AA) and paroxysmal nocturnal haemoglobinuria (PNH) are lacking altogether. As a consequence, this issue is either underevaluated or alternatively, instruments originally designed for cancer patients are being used. We therefore started to systematically develop a AA/PNH-specific QoL (QLQ-AA/PNH) instrument in these ultra-rare diseases according to European Organisation for Research and Treatment of Cancer (EORTC) guidelines. While phases I and II of the process have previously been published, we now report on the resulting instrument (phase III of this process). As part of the phase III of the evaluation process, we approached patients through physicians, patient support groups, and patient conferences. After participants completed the preliminary questionnaire and reported socio-demographic data, they were interviewed in person or via phone with a debriefing interview to find out whether the items were relevant, easy to understand, and acceptable to patients and whether there was anything missing in the questionnaire. We hypothesised what items could be combined into a scale and calculated Cronbach’s alpha to define its preliminary internal consistency. After definition of a priori criteria to keep or delete items, a group of six experts met in person, discussed the results, and decided on in- or exclusion. A total of 48 patients were enrolled, 21 of those suffered from AA (44%), 13 from PNH (27%), and 14 from AA/PNH syndrome (29%). The median time to complete the 69 items was 10 min (range 5–20), mean time 11 min. The compliance criterion (> 95% completion) was fulfilled by 57 items. Twenty-three items were mentioned as especially relevant by ≥ 2% of the patients. Cronbach’s alpha of the hypothesised scales ranged from 0.63 (social support) to 0.92 (fear of progression and illness intrusiveness). Finally, 47 items were kept; 16 were deleted, and 5 were changed, while 1 item expanded. This resulted in 54 items in total. As no issues were mentioned to lacking by a minimum of five patients, no items were added to the questionnaire. After completion, the AA/PNH-QoL tool (QLQ-AA/PNH) was translated according to EORTC guidelines into English, French, and Italian. For patients with PNH and AA until now, the standard assessment for QoL was to use the EORTC Quality of Life Questionnaire (QLQ-C30) or the Functional Assessment of Chronic Illness Therapy Fatigue Instrument (FACIT-Fatigue). We herewith present a new instrument aimed to be better tailored to the needs of PNH and AA patients. The anticipated fourth development phase will be performed for psychometric validation; however, we already explored the internal consistency of the hypothesised scales and found the results to be very good. Hence, the new QLQ-AA/PNH with 54 items can be used in trials and clinical studies from now on, according to EORTC strategy even if the scoring algorithm at this point is preliminary and the QLQ-AA/PNH might change slightly after phase IV. This is important, as there are no other disease-specific instruments available for AA/PNH patients right now.

Biosimilar filgrastim treatment patterns and prevention of febrile neutropenia: a prospective multicentre study in France in patients with solid tumours (the ZOH\xe9 study)

BackgroundThe ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT).MethodsPatients ≥ 18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines.ResultsResponses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ≥ 1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (< 10%) FN risk (‘over prophylaxis’). Nearly half of patients’ CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ≥ 2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed.ConclusionsUse of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians’ decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of < 10%.

Real-world use of granulocyte colony-stimulating factor in ambulatory breast cancer patients: a cross-sectional study.

To prevent febrile neutropenia (FN), European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend primary prophylaxis with granulocyte colony-stimulating factors (PPG) for patients at high risk (≥ 20%) of FN. In Belgium, the use of PPG is restricted by specific reimbursement criteria. The impact of these criteria on PPG use and adherence to guidelines is unknown. This multicentre, cross-sectional, observational study aimed to describe PPG use by FN risk category in breast cancer patients who were scheduled to receive myelosuppressive chemotherapy in outpatient clinics in Belgium during a 2-week period between 13 October and 12 December 2014. In total, 490 patients were enrolled. Median age was 57.0years. Based on their chemotherapy regimen, 53.9, 5.1 and 41.0% of patients were at a low, intermediate and high risk of FN, respectively. Overall, 39.8% of patients received PPG (17.0, 12.0 and 73.1% of those receiving low-, intermediate- and high-risk regimens, respectively). In the high-risk category, PPG was used in 89.9% of dose-dense and in 25.0% of classical chemotherapy regimens. PPG use was adherent to EORTC guidelines in 75.3% of patients (30.6% appropriate use, 44.7% appropriate non-use). EORTC guidelines would recommend PPG use in 46.1% of this study population (n = 226), and its use was reimbursable in Belgium in 76.1% of these patients (n = 172), but only 66.4% of them received PPG (n = 150). Both Belgian reimbursement criteria and physician decision-making led to a proportion of patients for whom PPG treatment was recommended but finally not receiving it.

International Psychometric Validation of an EORTC Quality of Life Module Measuring Cancer Related Fatigue (EORTC QLQ-FA12).

The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a new multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA13 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. The methodology follows the EORTC guidelines for phase IV validation of modules. This paper focuses on the results of the psychometric validation of the factorial structure of the module. For validation and cross-validation confirmatory factor analysis (maximum likelihood estimation), intraclass correlation and Cronbach alpha for internal consistency were employed. The study involved an international multicenter collaboration of 11 European and non-European countries. A total of 946 patients with various tumor diagnoses were enrolled. Based on the confirmatory factor analysis, we could approve the three-dimensional structure of the module. Removing one item and reassigning the factorial mapping of another item resulted in the EORTC QLQ-FA12. For the revised scale, we found evidence supporting good local (indicator reliability ≥ 0.60, factor reliability ≥ 0.82) and global model fit (GFI t1|t2 = 0.965/0.957, CFI t1|t2 = 0.976/0.972, RMSEA t1|t2 = 0.060/0.069) for both measurement points. For each scale, test-retest reliability proved to be very good (intraclass correlation: R t1-t2 = 0.905-0.921) and internal consistency proved to be good to high (Cronbach alpha = .79-.90). Based on the former phase III module, the multidimensional structure was revised as a phase IV module (EORTC FA12) with an improved scale structure. For a comprehensive validation of the EORTC FA12, further aspects of convergent and divergent validity as well as sensitivity to change should be determined.

How to evaluate sexual health in cancer patients: development of the EORTC sexual health questionnaire for cancer patients.

BackgroundThe aim of the study is to describe the development of a comprehensive European Organisation for Research and Treatment of Cancer (EORTC) questionnaire to assess sexual health of female and male cancer patients and for cancer survivors.MethodsAccording to the EORTC guidelines, the development of an EORTC sexual health questionnaire is typically organised in four phases. The first phases comprise a literature search following interviews with patient and health care professionals (HCPs) (phase 1) and the operationalization into items (phase 2). The translation process is formally conducted according to the EORTC QLG Translation guidelines with a rigorous forward-backward procedure supported by native speakers.ResultsStudies on sexuality in oncology patients which were identified by a literature search predominantly focused on issues of activity, experiences of sexual dysfunction, and satisfaction with sexual functioning. The literature review identified themes beyond these aspects. In total 53 potentially relevant issues were presented to 107 patients and 83 HCPs, different evaluations were found.ConclusionsA questionnaire that includes physical, psychological, and social aspects of sexuality of cancer survivors will be needed. Pre-testing and validation of the questionnaire will be done in future (phases 3 and 4). Divergent ratings of patients and professionals should be further investigated.

Content validity and legacy patient-reported outcome measures in cancer.

The publication in 2009 of the Guidance for Industry by US Food and Administration (FDA) [1] ushered in a significant change in the way patient-reported outcome measures (PROMs) are evaluated when used by pharmaceutical companies to support product label claims. In particular, the FDA Guidance emphasised patient input in the development of PROMs. To underline this point, a review of the reasons for FDA rejections of PRO label claims [2] concluded that just under 40 % of all rejections were due to the PROM not being fit for purpose; 31 % of product PRO claims were rejected due to a lack of content validity. This approach adopted by the FDA may be problematic for those legacy PROMs whose development predates the Guidance, one of which is the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 [3]. There is no evidence that the early development of the EORTC QLQ-C30 incorporated patient involvement in the content validity other than in rating the acceptability of items. Despite this, the instrument continues to be widely used in oncology clinical trials: a search on clinicaltrials.gov for the period 1 January 2009 to 31 December 2013 revealed 207 registered trials that included the EORTC QLQ-C30. Furthermore, its inclusion has been recommended in comparative effectiveness research [4], and it has been shown to be of use in facilitating patient–clinician communication [5]. Beyond that the instrument has been part of a successful PRO product label claim granted by the FDA [6] after the publication of the Guidance document. Content validity is one particular psychometric property of the EORTC QLQ-C30 that has not been revisited since the early development of the instrument. Although the EORTC QLQ-C30 has been subsequently validated with other cancer diagnoses, it has undergone little or no change in terms of the original content. However, this needs to be balanced against the fact that the EORTC QLQ-C30 has been completed by thousands of patients with different types of cancers since its development. There are currently 31 studies registered on the EORTC clinical trials database with a total target recruitment of 29,106 patients across a spectrum of cancers including brain, breast, (paediatric) leukaemia, endocrine, gastrointestinal, genito-urinary, gynaecological, head and neck, lung, and melanoma (www.eortc.org/clinical-trials). It also should be stressed that the EORTC guidelines for the development of diseasespecific modules emphasise the necessity of patient input in order to enhance content validity [7]. It could therefore be argued that the EORTC QLQ-C30 has been subjected to a content validation process through exposure in numerous clinical trials, particularly given that the domains of the instrument, such as fatigue, sleeplessness, pain, appetite loss, nausea, and cognitive problems largely correspond with the core set of symptoms recommended for assessment by the National Cancer Institute’s Symptom Management & Health-related Quality of Life Steering Committee [8]. It remains for future research to determine whether the EORTC QLQC30 requires further modification or is—in its current form and owing to the significant post-development use across different cancers and treatments—fit for purpose in oncology trials. A. B. Smith (&) York Health Economics Consortium, Market Square, University of York, York YO10 5NH, UK e-mail: adam.smith@york.ac.uk

Good Usage of Biosimilar Filgrastim: A Subanalysis of the Next Study

▪IntroductionFebrile neutropenia (FN), a major risk factor for morbidity/mortality, is associated with dose delays and/or reductions in potentially cytotoxic chemotherapy (CT) regimens. It is defined as an oral temperature >38.5°C, or two consecutive readings of >38.0°C for 2 h, with an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L. Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend prophylactic use of granulocyte-colony stimulating factor (G-CSF) when using a CT regimen associated with a >20% risk of FN or in less intensive CT regimens if certain risk factors (eg >65 years, advanced disease, history of prior FN) are present. Biosimilar filgrastim (Nivestim™, Hospira Inc.) is a G-CSF licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. As the NEXT (Nivestim™ safety profile in patiEnts treated with cytotoXic chemotherapy in real-life clinical pracTice) study was conducted in France, the real-life usage of biosimilar filgrastim is compared with that recommended by current EORTC guidelines.MethodsThe NEXT study was a prospective, non-interventional, longitudinal, multicentre, national study. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Secondary objectives included the description of patients (pts) treated with, and patterns of use of, biosimilar filgrastim.Adult pts undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as primary or secondary prophylaxis, or as curative treatment, were included. The subanalysis presented here included only pts receiving prophylactic biosimilar filgrastim. Data were recorded on case report forms and included pt characteristics (demographics, medical history, CT-related data), biosimilar filgrastim treatment-related data (indication, dose, route of administration, treatment initiation) and treatment-emergent AEs, including FN. Individual FN risk factors were analysed. Pts were monitored for 1–6 CT cycles at three visits: inclusion, a follow-up visit during treatment and the final visit following CT.ResultsOverall, 2102 pts were included in the study analysis and 2065 pts received prophylactic biosimilar filgrastim. At inclusion, 73.9% of pts had no prior FN. Of the pts included in this analysis, 19.4% received CT associated with a high risk of developing FN (intermediate risk: 55.6%; low risk: 25.0%). Of the pts receiving CT regimens associated with an intermediate risk of FN, 95.4% had ≥1 risk factor for FN and of those receiving a regimen associated with a low risk of FN, 96.5% had ≥1 FN risk factor (Table 1).Of all pts receiving prophylactic biosimilar filgrastim, 3.5% developed FN after the first CT cycle, 1.8% developed an infection and 2.4% were hospitalised for FN and/or infection after the first CT cycle. Median time to initiation of biosimilar filgrastim was 2 days after the last CT dose; mean treatment duration ± SD was 6.0±3.8 days. Anti-infective prophylaxis was reported in 14.5% of pts.ConclusionThe majority of pts received prophylactic biosimilar filgrastim according to EORTC guidelines (ie either had >20% risk of FN or had ≥1 FN risk factor). Biosimilar filgrastim (Nivestim™) is an alternative therapeutic option for pts with prophylactic CT-induced neutropenia.Table 1Proportion of patients with risk factors for FNRisk factorPatients (%)Chemotherapy regimen associated with a high risk(>20%) of FNChemotherapy regimen associated with an intermediate risk (10–20%) of FNChemotherapy regimen associated with a low risk(<10%) of FNFemale51.558.647.9Age >65 years35.940.255.9Advanced disease40.441.966.4≥1 severe comorbidity25.627.535.2Poor nutritional status*3.83.17.0WHO performance grade ≥30.00.10.3Haemoglobin <12 g/dL at inclusion37.739.150.9Concomitant radiotherapy2.32.85.0Prior FN7.66.111.5*Defined as a body mass index <18.5 kg/m2WHO, World Health Organization DisclosuresMaloisel:Pfizer: Research Funding; Novartis: Research Funding; Hospira: Research Funding; Amgen: Research Funding. Albrand:Hospira: Employment.

Recommended Usage of Epoetin Alpha Biosimilar Retacrit™: A Subanalysis of the Orheo Study

IntroductionChemotherapy-induced anaemia (CIA) is a frequent complication of patients (pts) with cancer, associated with fatigue and impaired quality of life, and may have serious medical consequences that can lead to discontinuation or interruption of chemotherapy (CT). Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend epoetin treatment of CIA to increase haemoglobin (Hb) levels and to help to prevent red blood cell transfusions and related complications. Several epoetin alpha biosimilars are currently approved for use in the EU for the treatment of CIA. The ORHEO study (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France that evaluated the changes in Hb level in pts with solid tumours, lymphoma or myeloma, treated with an epoetin alfa biosimilar (EAB). In this subanalysis of the ORHEO study, we compare the usage of EAB in relation to the dosage recommendations of the EORTC guidelines, with respect to efficacy and safety.MethodsPts >18 years with CIA (Hb <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for EAB treatment were included in this study. Pts were monitored at the start of EAB therapy (D0), at 3 months (M3) and 6 months (M6). Hb response was defined as achievement of target Hb without blood transfusions in the preceding 3 weeks and during treatment or Hb ≥10 g/dL or Hb increase ≥1 g/dL since inclusion. The prescribed dosage of EAB according to body weight and the tolerability of EAB at that recommended dosage were analysed at each time point.ResultsData from 2310 pts (mean age ± standard deviation 66.5±11.8 years) from 232 centres were included in the study analysis. Overall, 79.6% of pts had solid tumours, 13.0% had lymphoma and 7.4% myeloma. Of those pts with solid tumours, 30.1% of pts had a stage III and 21.6% had a stage IV tumour. Mean baseline Hb level across all pts was 9.6 g/dL, with 35.6% of pts having moderate anaemia (Hb 8–9.5 g/dL).Almost all pts (99.9%) received the epoetin alpha biosimilar (Retacrit™, Hospira UK Ltd., median dose 30,000 IU/week). Overall, 43.8% of pts received the recommended dose of EAB (as determined by their weight) throughout the study. The proportion of pts receiving the recommended dose showed little variation between malignancies (lymphoma: 43.6%; myeloma: 40.9%; breast: 39.3%; lung: 48.3%; colorectal: 39.5%). Overall, the percentage of responders was 81.6% at M3 and 86.5% at M6. The overall mean change in Hb level was 1.5±1.6 g/dL at M3 and 1.72±1.61 g/dL at M6. Responses to treatment at M6 were similar whether or not EAB was prescribed at the recommended dose throughout the study. A similar proportion of pts receiving the recommended dose of EAB reported adverse events (AEs) at M6 compared with pts who did not receive the recommended dose (9.9 vs 9.0%). Overall, transfusion rates were 9.4% and 5.8%, while the rate of thromboembolic events was 2.4% and 1.5%, at 3 and 6 months respectively.ConclusionIn the ORHEO study, 44% of pts received the EORTC recommended dose of EAB over the 6-month course of the study. However, the response to therapy was similar regardless of dose. Furthermore, the frequency of overall AEs at M6 did not vary depending on dose.In conclusion, the EAB Retacrit™ was effective and well tolerated in the management of CIA in pts with solid tumours, lymphoma and myeloma and provides an alternative therapeutic option for the treatment of CIA. DisclosuresMichallet:MSD: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hospira: Consultancy, Honoraria. Soubeyran:Roche: Honoraria; Celgene: Honoraria; Mundipharma: Honoraria; Hospira: Honoraria. Kurtz:Hospira: Coverage of travel expenses/congress fees Other. Albrand:Hospira: Employment.

The EORTC emotional functioning computerized adaptive test: phases I–III of a cross‐cultural item bank development

BackgroundThe European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is currently developing computerized adaptive testing measures for the Quality of Life Questionnaire Core-30 (QLQ-C30) scales. The work presented here describes the development of an EORTC item bank for emotional functioning (EF), which is one of the core domains of the QLQ-C30.MethodsAccording to the EORTC guidelines on module development, the development of the EF item bank comprised four phases, of which the phases I–III are reported in the present paper.Phase I involved defining the theoretical framework for the EF item bank and a literature search. Phase II included pre-defined item selection steps and a multi-stage expert review process. In phase III, feedback from cancer patients from different countries was obtained.ResultsOn the basis of literature search in phase I, a list of 1750 items was generated. These were reviewed and further developed in phase II with a focus on relevance, redundancy, clarity, and difficulty. The development and selection steps led to a preliminary list of 41 items. In phase III, patient interviews (N = 41; Austria, Denmark, Italy, and the UK) were conducted with the preliminary item list, resulting in some minor changes to item wording. The final list comprised 38 items.DiscussionThe phases I–III of the developmental process have resulted in an EF item list that was well accepted by patients in several countries. The items will be subjected to larger-scale field testing in order to establish their psychometric characteristics and their fit to an item response theory model.

The early development phases of a European Organisation for Research and Treatment of Cancer (EORTC) module to assess patient reported outcomes (PROs) in women undergoing breast reconstruction

IntroductionA comprehensive evaluation of breast reconstruction (BRR) surgery includes measurement of patient reported outcomes (PROs). There is, however, a lack of validated BRR-specific PRO measures (PROMs) that adequately assess relevant issues. This study is developing a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire/module specific for PROs in BRR to supplement the cancer-core and breast cancer EORTC questionnaires, respectively: the QLQ-C30 and QLQ-BR23. MethodsPhases I and II of questionnaire development followed EORTC guidelines including a systematic literature review to identify all potential ‘issues’ (concepts relevant to PROs) and semi-structured interviews with 89 patients and 9 European multi-disciplinary health care professionals (HCPs) (Sweden, Italy and the United Kingdom [UK]). Interviewers asked participants the ‘relevance’ of outcomes identified in the literature and captured additional ‘issues’ of importance. ResultsThe literature search and interviews of patients and HCPs yielded 69 issues relating to BRR operationalised into 31 provisional items (single questions) for the module, which was conceptualised to contain five scales: treatment/surgery related symptoms (affecting the shoulder, arm and reconstructed breast), body image, sexuality, cosmetic outcomes (pertaining to three areas: breast, donor site and nipple) and overall satisfaction. DiscussionThe provisional development of the EORTC BRR module has 31 items addressing issues of importance to patients as well as HCPs. Further international testing is underway as a UK National Cancer Research Network trial to ensure that this PROM will be psychometrically and clinically robust and applicable for use in clinical trials, cohort studies, national audit and clinical practice.

Development of an EORTC quality of life phase III module measuring cancer‐related fatigue (EORTC QLQ‐FA13)

European Organisation for Research and Treatment of Cancer (EORTC) has developed a new multidimensional instrument measuring cancer-related fatigue that can be used in conjunction with the quality of life core questionnaire, EORTC QLQ-C30. The paper focuses on the development of the phase III module, collaborating with seven European countries, including a patient sample of 318 patients. The methodology followed the EORTC guidelines for developing phase III modules. Patients were assessed by questionnaires (EORTC QLQ-C30 with the EORTC Fatigue Module FA15) followed by an interview, asking for their opinions on the difficulty in understanding, on annoyance and on intrusiveness. The phase II FA15 was revised on the basis of qualitative analyses (comments of the patients), quantitative results (descriptive statistics) as well as the multi-item response theory analyses. The three dimensions (physical, emotional and cognitive) of the scale could be confirmed. As a result, EORTC QLQ-FA13 is now available as a valid phase III module measuring cancer-related fatigue in clinical trials and will be psychometrically improved in the upcoming phase IV.

Health-related quality of life in patients with lung cancer: Validation of the Mexican-Spanish version and association with prognosis of the EORTC QLQ-LC13 questionnaire

IntroductionLung cancer (LC) is the first cause of cancer-related mortality worldwide and health-related quality of life (HRQL) is a fundamental outcome for evaluating treatment results. Our objective was to validate the Mexican-Spanish versions of the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life QLQ-LC13 disease-specific questionnaire module in Mexican patients with LC; and to explore the possible prognostic role of HRQL data. MethodsTranslation procedures followed EORTC guidelines. Both instruments were completed by patients with LC. Tests for reliability and validity were performed. A subset of patients was administered HRQL evaluations before and after chemotherapy. HRQL was associated with prognosis in chemotherapy-naïve patients. The protocol was approved by the Institute's Ethics Committee. ResultsOne hundred fifty three patients (mean age, 60.3 years; 84 females and 69 males) completed both questionnaires. Compliance rates were high, and the questionnaires were well accepted. Nine of 10 multi-item scales of both questionnaires presented Cronbach's alpha coefficients>0.7. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Patients with better Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status reported better functional HRQL scores. Different scales in the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires were accurately related with clinical characteristics. Functional as well as disease-symptom scales improved after chemotherapy, but treatment side-effects scales worsened in test–retest analysis. Better role functioning and absence of thoracic pain scales were associated with longer overall survival (OS) (p=0.009 and p=0.035, respectively). ConclusionThe Mexican-Spanish versions of the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires are reliable and valid for HRQL measurement in Mexican patients with LC and can be used in clinical trials.

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (⩾65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (⩾20%) or intermediate (10–20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10–20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem.

Promoting evidence-based management of anemia in cancer patients: concurrent and discriminant validity of RESPOND, a web-based clinical guidance system based on the EORTC guidelines for supportive care in cancer

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. 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). 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. 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.

Implications of the European Organisation for Research And Treatment Of Cancer (EORTC) Guidelines on the Use of Granulocyte Colony-Stimulating Factor (G-CSF) for Lymphoma Care

Febrile neutropenia (FN) is a potentially life-threatening complication of myelosuppressive chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend use of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis if the overall FN risk to a patient is >or=20%, or if a reduction in chemotherapy dose intensity correlates with a poorer outcome. Many of the regimens used for treatment of lymphoma, including R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone), are associated with an FN risk of approximately 20% or higher. Individual patient factors that may increase the risk of FN such as advanced age or advanced disease should be taken into account when assessing the need for G-CSF support. Predictive models are being developed to facilitate individual risk assessment. Additional anti-infective prophylaxis may be indicated in some settings. There is now much evidence for the benefits of G-CSF in reducing the incidence of FN and facilitating delivery of chemotherapy, including dose-escalated and dose-dense (interval-reduced) regimens. If given according to guidelines, G-CSF has the potential to reduce FN and related morbidity. Furthermore, by facilitating delivery of planned chemotherapy, use of G-CSF may potentially influence survival in the curative setting. Implementation of the EORTC guidelines will lead to a greater proportion of patients receiving G-CSFs, but the costs involved should be at least partly offset by a reduction in FN and its associated costs, including those of hospitalization.

Promoting evidence-based management of anemia in cancer patients: Background and scientific validation of RESPOND, a web-based clinical decision support system

19676 Background: The 2006 European Organisation for Research and Treatment of Cancer (EORTC) guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. To promote clinicians’ adoption of evidence- based (EB) practice guidelines (EBPGs), it is critical to bring guidelines to the point of care. RESPOND is an EB clinical decision support system (CDSS) based on the EORTC guidelines. CDSSs are seldom validated. We describe the methodologies of two studies being conducted to validate RESPOND. Methods. Study 1: descriptive design - accuracy and content validity. Five experts are asked to rate the accuracy of algorithms derived from the guidelines; the objective being an intraclass correlation coefficient =0.90 for each of 27 algorithmic sets. Study 2: hybrid matched pre-post design - concurrent and discriminant validity. Two patient cohorts (n=33 each) matched by type of cancer and similarity of chemotherapy regimen ie, sample 1 (4 months prospective data after RESPOND [post]) and sample 2 (4 months retrospective data prior to RESPOND [pre]) were used to test concurrent validity (congruence scores [CS] of sample 1) and discriminant validity (difference between sample 2 and sample 1 CS). A score is calculated for each patient to quantify the extent to which treatment and outcomes are congruent with the EORTC EBPG. Table 1 . Calculation of the congruence score ESA, erythropoiesis-stimulating agent; Hb, hemoglobin, Q1W, once weekly, Q3W, once every three weeks Conclusions. These studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool. [Table: see text] [Table: see text]

Response to the publication: EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer

The guidelines issued recently by the European Organisation for Research and Treatment of Cancer (EORTC) for the management of cancer-related anaemia [1] are a welcome addition to previously published guidelines [2]. In recent years the impact of anaemia on patient outcomes and quality of life (QOL) has been highlighted vis-à-vis the availability of effective anaemia treatments beyond blood transfusion. The recognition that anaemia and resulting fatigue are not inevitable consequences of cancer treatment, and that performance status and QOL are improved when anaemia is controlled, is a great stride forward.