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Management of Cancer-Related Anemia in Patients with Breast or Gynecologic Cancer: New Insights Based on Results from the European Cancer Anemia Survey

^a Velindre Cancer Centre, Whitchurch, Cardiff, United Kingdom; ^b Universitätsklinikum Hamburg-Eppendorf, Germany; ^c Hospital Clinic, Barcelona, Spain; ^d Leiden University Medical Center, Leiden, The Netherlands; ^e Centre Antoine-Lacassagne, Nice, France; ^f ZNA Middelheim, Antwerp, Belgium; ^g University Hospital, Ghent, Belgium

Key Words. Breast cancer • Gynecologic cancer • ECAS • Anemia

Correspondence: Peter J. Barrett-Lee, M.D., Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, United Kingdom. Telephone: 44-29-20-615-888; Fax: 44-29-203-16-267;-mail: peter.barrett-lee{at}velindre-tr.wales.nhs.uk

Received April 14, 2005; accepted for publication August 15, 2005.

	LEARNING OBJECTIVES

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After completing this course, the reader will be able to:

1. Discuss the negative impact of anemia and its sequelae, particularly fatigue, in patients with breast or gynecologic cancer.
   
2. Describe the results of the European Cancer Anemia Survey (ECAS), which defined the prevalence, incidence, and treatment of anemia in the European cancer community, identified anemia risk factors, and demonstrated that anemia is often suboptimally treated.
   
3. Explain how the successful management of anemia is associated with patient well-being and improved overall quality of life.
   

	ABSTRACT

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The incidence, prevalence, and treatment of anemia (hemoglobin [Hb] <12 g/dl) in women with breast cancer and gynecologic cancer were evaluated using data from the European Cancer Anemia Survey (ECAS). Adult patients with newly diagnosed treated or untreated disease, persistent/recurrent disease, and disease in remission were enrolled and followed for up to six chemotherapy cycles or six evaluation points within a 6-month period. At enrollment, 30.4% of breast cancer patients and 49.1% of gynecologic cancer patients were anemic. A significant correlation was shown between low Hb level and poor performance status (World Health Organization criteria) at enrollment for both breast cancer and gynecologic cancer patients. In all, 62.4% of breast cancer patients and 81.4% of gynecologic cancer patients were anemic at some time during the survey. The incidence of anemia, determined in a carefully defined population, was 59.8% for breast cancer patients and 74.8% for gynecologic cancer patients. Despite the high prevalence and incidence of anemia, only 26.3% and 42.7% of patients in the respective groups received anemia treatment. In breast cancer patients, the mean Hb trigger was 10 g/dl for epoetin treatment and 8.6 g/dl for transfusion; corresponding values for gynecologic cancer patients were 10.1 g/dl and 9.1 g/dl. Logistic regression analyses in the overall ECAS population identified five factors as significant and suitable predictors of anemia: lower initial Hb, having lung or gynecologic cancer versus gastrointestinal/colorectal cancer, any other cancer versus gastrointestinal/colorectal cancer, treatment with platinum chemotherapy, and being female. The ECAS data highlight the need for greater awareness of the adverse impact of anemia on cancer patients and for optimal anemia management to ensure maximal patient quality of life.

	INTRODUCTION

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The incidence of breast cancer in women in Europe is high (n = 346,118), as are the incidences of uterine (n = 73,148), cervical (n = 64,929), and ovarian (n = 60,916) cancer [1]. These malignancies result in significant morbidity and mortality. Many of these patients, especially those with gynecologic cancer (uterine, cervical, ovarian), become anemic as a result of their disease or its treatment or experience treatment-related exacerbations of existing anemia [2, 3]. Anemia, in turn, leads to a wide array of symptoms that can negatively affect patients’ physical status and functional capacity, and subsequently impair their quality of life (QoL). Notable among these symptoms are fatigue, dyspnea, palpitations and other cardiovascular complications, cognitive dysfunction, depression, nausea, sexual/reproductive dysfunction, and impaired immune function [4, 5]. Anemia and its most common symptom, fatigue, are of particular concern in the management of patients with breast cancer and gynecologic cancer because these malignancies frequently develop in younger women who are usually in their most productive years, often dealing with advancing careers and families [6]. However, anemia and fatigue are also problematic in older patients, whose overall health and functional capacity tend to be more compromised than those of younger patients and whose status may be further impaired by these symptoms. Unfortunately, the impact of anemia and fatigue is often underappreciated, even though fatigue has been reported by cancer patients as the most disturbing of all physical symptoms they experience [7, 8].

That the impact of anemia is not always fully appreciated is highlighted by the results of the European Cancer Anemia Survey (ECAS). A large, prospective, epidemiologic, observational study conducted in 24 European countries, ECAS enrolled and collected data on more than 15,000 patients with various solid and hematologic malignancies treated at 748 academic, community, and private centers specializing in cancer care. The objective of the survey was to determine the prevalence and incidence of cancer-related anemia, anemia management practices, and risk factors for anemia development in the European cancer community. Importantly, ECAS not only demonstrated the high prevalence and incidence of cancer-related anemia but also revealed that anemia treatment was often suboptimal, either not being offered at all or being initiated only after the patient’s hemoglobin (Hb) level had dropped to a mean of 9.7 g/dl [9]. Moreover, for one third of chemotherapy patients who received epoetin and for more than half of chemotherapy patients who received transfusion, anemia treatment was not offered until their Hb levels had declined to <9 g/dl.

Included in the ECAS population were a substantial number of patients with either breast cancer or gynecologic cancer. This report analyzes the data from these two patient populations to better define the prevalence, incidence, and treatment of anemia in these groups, thereby providing a basis for evidence-based decisions regarding anemia management. The breast cancer and gynecologic cancer patients were considered together in this report because these populations were similar demographically (all female patients), and comparisons could be made for anemia rates and changes in Hb levels over time, World Health Organization (WHO) performance scores, and anemia treatment, covering the range of platinum (usual in gynecologic cancer patients) and nonplatinum (usual in breast cancer patients) chemotherapy.

	MATERIALS AND METHODS

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Full details of the methods used for ECAS are provided elsewhere [9]. Briefly, patients enrolled in the survey, from January through July 2001, were followed for as many as 6 months and were 18 years of age or older with a diagnosis of a solid tumor or hematologic malignancy. Patients were eligible regardless of their disease status or the type of cancer treatment they received. Additionally, they were to be under the care of a physician or center specializing in cancer treatment but could not be enrolled in a clinical trial.

Data were collected at enrollment, at 6 evaluation points or monthly for 6 months at regular scheduled clinic visits, and at survey completion. Data collected included age, gender, tumor type (International Classification of Diseases–9th Revision [ICD-9] code) and stage, date of initial diagnosis, disease status, performance status, and laboratory values (including Hb and hematocrit). Also, cancer treatment and anemia therapy (transfusion, epoetin [either epoetin alfa (Eprex^®/Epypo^®; Ortho Biotech/Janssen-Cilag, High Wycombe, United Kingdom, http://www.orthobiotech.co.uk; Procrit^®; Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.orthobiotech.com) or epoetin beta (NeoRecormon^®; Hoffmann-La Roche, Basel, Switzerland, http://www.roche.com)], iron) were recorded, as were the current cycle number for patients receiving chemo-therapy, final chemotherapy, and radiotherapy regimens, and reason for survey completion (end of survey period, death, lost to follow-up, early withdrawal). Performance scores were based on the WHO scale, in which 0 is the best possible score and 4 is the worst possible score. Anemia (Hb <12 g/dl) was categorized as mild (11.9–10 g/dl), moderate (9.9–8 g/dl), or severe (<8.0 g/dl), based on the Common Toxicity Criteria, National Cancer Institute [10] and the European Organization for Research and Treatment of Cancer (EORTC).

Data from all participating countries were pooled for statistical analysis. Sample characteristics and baseline Hb levels were examined with descriptive statistics. Two-way analyses of variance models were used to determine WHO performance status score at enrollment from Hb level at enrollment, treatment status at enrollment, and interaction between Hb level and treatment status. Additionally, the data were analyzed to identify independent risk factors that could be used to develop a clinically applicable predictive risk model for chemotherapy-related anemia. Potential predictors were evaluated in bivariate analyses with the outcome measure (anemia) to obtain unadjusted odds ratios (ORs) and then entered into a multivariate logistic regression equation to evaluate the predictors and develop adjusted odds ratios (AORs). Each factor was assigned an Anemia Risk Value that could be added to others to provide a Total Anemia Risk Score for predicting anemia development.

	RESULTS

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Patients
The ECAS was conducted between January 2001 and July 2001 and concluded in February 2002 to allow for 6 months of evaluation after the last patients were enrolled. A total of 15,367 patients was enrolled, including 3,253 women with breast cancer and 1,741 women with gynecologic cancer (ovarian, n = 1,173; cervical, n = 289; other, n = 279). The mean age at enrollment was slightly lower for breast cancer patients (54.1 years; range, 21–93) than for gynecologic cancer patients (57.6 years; range, 18–89). This difference mainly reflected the higher proportion of patients aged 18–49 years in the breast cancer group (35.5%) compared with the gynecologic cancer group (24%). At enrollment, breast cancer and gynecologic cancer patients were similar with respect to disease status as 32.7% of patients with breast cancer and 39.2% of patients with gynecologic cancer were newly diagnosed and not receiving cancer treatment, whereas 24.8% and 18.9% of patients in the respective groups were newly diagnosed and receiving treatment; 30% of breast cancer patients and 36% of gynecologic cancer patients were experiencing persistent or recurrent disease, and 12.5% and 5.9%, respectively, were in remission. Treatment patterns were also similar between breast cancer and gynecologic cancer patients at enrollment: 53.8% of breast cancer patients and 58.4% of gynecologic cancer patients had received neither chemotherapy nor radiotherapy; 36.9% and 35.7%, respectively, had received chemotherapy; 5.9% and 3.5%, respectively, had received radiotherapy; and 3.4% and 2.4%, respectively, had received concomitant chemotherapy and radiotherapy.

Anemia Prevalence and Incidence
More gynecologic cancer (49.1%) than breast cancer (30.4%) patients were anemic (Hb <12 g/dl) at enrollment, and more gynecologic cancer (12.7%) than breast cancer (4.3%) patients had moderate to severe anemia (Hb 9.9 g/dl) at that time (Fig. 1). Overall, 62.4% (1,802/2,890) of breast cancer patients and 81.4% (1,272/1,563) of gynecologic cancer patients were anemic at some time during the survey. Among the breast cancer patients (n = 3,071), those with persistent/recurrent disease were the most frequently anemic (41.7%), followed by newly diagnosed patients receiving chemotherapy (33.9%), patients in remission (22.6%), and newly diagnosed patients who had not received chemotherapy (20.4%) (Table 1). In the gynecologic cancer group (n = 1,662), anemia occurred most frequently in patients with persistent/recurrent disease (57.5%), followed by newly diagnosed patients receiving chemotherapy (52.4%), newly diagnosed patients not receiving chemotherapy (41%), and patients in remission (40.8%) (Table 1).

View larger version (14K): [in this window] [in a new window]   Figure 1. Hemoglobin level at enrollment by diagnostic group (analysis populations).

View larger version (16K): [in this window] [in a new window]   Figure 2. Mean hemoglobin level at enrollment and by cycle: breast cancer incidence population. Patients in incidence population with full-cycle data available.

View larger version (16K): [in this window] [in a new window]   Figure 3. Mean hemoglobin level at enrollment and by cycle: gynecologic cancer incidence population. Patients in incidence population with full-cycle data available.

View larger version (14K): [in this window] [in a new window]   Figure 4. Hemoglobin nadir for breast and gynecologic cancer patients with anemia at any time during the survey.

View larger version (20K): [in this window] [in a new window]   Figure 5. Hemoglobin at enrollment by World Health Organization scores at enrollment. Abbreviation: CI, confidence interval.

Anemia Treatment
Of the 1,802 patients with breast cancer (62.4%) and the 1,272 patients with gynecologic cancer (81.4%) who were anemic at any time during the survey, 26.3% and 42.7%, respectively, received treatment for their anemia. Overall, 11.6% of breast cancer patients and 16.5% of gynecologic cancer patients received epoetin alone or in combination with iron supplementation and/or transfusion; treatment for the remaining patients consisted of iron supplementation alone (breast cancer, 7.3%; gynecologic cancer, 10.9%) or transfusion alone or with iron supplementation (breast cancer, 7.4%; gynecologic cancer, 15.3%). The mean Hb levels for initiation of first anemia treatment in breast cancer patients were 10 g/dl (95% confidence interval [CI], 9.81–10.23) for patients receiving epoetin and 8.6 g/dl (95% CI, 8.41–8.79) for those receiving transfusions. Corresponding Hb values for the initiation of anemia treatment for gynecologic cancer patients were 10.1 g/dl (95% CI, 9.88–10.31) for patients receiving epoetin and 9.1 g/dl (95% CI, 8.86–9.28) for those receiving transfusions.

Table 4 shows the percentage of patients who received different anemia treatment (or no treatment) according to Hb nadir; patients were receiving chemotherapy for newly diagnosed cancer or persistent/recurrent disease. Among breast cancer patients who received anemia treatment, those with more serious anemia, that is, Hb 9.9 g/dl, received transfusions more often than epoetin regardless of whether they were newly diagnosed (66.7% versus 24.2%, respectively) or had persistent/recurrent disease (83.3% versus 58.3%). Of those patients who were newly diagnosed and received only iron, 14% had Hb nadirs of 9–9.9 g/dl, while none had nadirs <9 g/dl; in comparison, 14.3% of patients with persistent/recurrent disease who received iron only had Hb nadirs <9 g/dl and another 28.6% had Hb nadirs of 9–9.9 g/dl. Of those patients with persistent/recurrent breast cancer who did not receive anemia treatment, nearly 20% had Hb nadirs 9.9 g/dl. The same general pattern of anemia treatment with transfusion or epoetin was noted for patients with gynecologic cancer. Gynecologic cancer patients with more serious anemia, that is, Hb levels 9.9 g/dl, received transfusions more often than epoetin irrespective of disease status; treatment rates for transfusions and epoetin in newly diagnosed patients were 85% versus 50%, respectively, and in patients with persistent/recurrent disease, they were 83.5% and 58.6%, respectively. For patients with newly diagnosed gynecologic cancer who received only iron, 13.8% had Hb nadirs <9 g/dl, and 27.6% had Hb nadirs of 9–9.9 g/dl. For patients with persistent/recurrent gynecologic cancer, 37.5% who received only iron had Hb nadirs <9 g/dl and 32.1% had Hb nadirs of 9–9.9 g/dl. Over 16% of newly diagnosed patients who did not receive anemia treatment had Hb nadirs 9.9 g/dl, as did over 30% of patients with persistent/recurrent disease.

	DISCUSSION

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Of the total population enrolled in the ECAS, more than 21% had breast cancer, and another 11% had gynecologic cancer. Thus, the ECAS data reported here constitute a broad, reliable base for making decisions regarding the general breast and gynecologic cancer populations in Europe.

The data from ECAS confirmed the high prevalence and incidence of anemia in breast cancer and gynecologic cancer patients suggested by a growing body of evidence over the past decade. Overall, nearly one third of breast cancer patients and one half of gynecologic cancer patients were anemic at enrollment. Included among these were 22.6% of breast cancer patients and 40.8% of gynecologic cancer patients whose disease was in remission—rates that were very similar to those for newly diagnosed but as-yet-untreated breast cancer (20.4%) and gynecologic cancer (41.0%) patients. As with other cancer patients, this high prevalence reflects the multifactorial etiology of anemia, which can occur as a result of the disease itself, cancer treatment, type, stage, and duration of the malignancy, surgical intervention, intercurrent infections, iron deficiency, and other factors [12]. Also, in younger patients, menstruation may lead to lower Hb levels, but the impact of this is unclear since many breast cancer and gynecologic cancer patients undergo treatment-related premature menopause.

The prevalence of anemia in breast cancer patients at any time during the survey was twice that observed at enrollment, while the prevalence in gynecologic cancer patients anemic at any time was 30% higher than at enrollment. The incidences of anemia in breast cancer and gynecologic cancer patients who were not anemic at enrollment received their first chemotherapy treatment during the survey and became anemic during this period were approximately 60% and 75%, respectively. The higher incidence of anemia in gynecologic cancer patients was to be expected, as the majority of these patients received platinum-based therapy, which is associated with clinically important decreases in Hb levels [2]. In both diagnostic groups, the incidence of anemia increased with increasing cycles of chemotherapy, although the development of anemia occurred more rapidly in gynecologic cancer patients, as shown by both cycle data and time to Hb nadir.

Interestingly, in the breast cancer population, anemia occurred in substantially more patients with persistent/ recurrent disease (who presumably were receiving second- or third-line chemotherapy), compared with newly diagnosed patients being treated for their cancer, most of whom were probably receiving adjuvant therapy. Factors that may have contributed to this difference include the older age of the patients with persistent/recurrent disease, who probably have more comorbid conditions; greater bone marrow involvement with advancing disease; [13] and greater use of taxanes, which are known to produce a high incidence of anemia both when administered alone and when given in combination with conventional chemotherapeutic agents [2].

In both breast cancer and gynecologic cancer patients, a lower Hb level correlated significantly (breast cancer, p <.001, R = –0.16; gynecologic cancer, p <.001, R = –0.18) with a worse functional status (WHO score of 3 or 4). This relationship was particularly noteworthy in gynecologic cancer patients with Hb levels <8 g/dl, whose frequency of WHO scores of 3 and 4 was twice that of breast cancer patients with Hb levels <8 g/dl. The underlying reason for the more severe impact of a low Hb level on functional (performance) status in the gynecologic cancer patients is unclear but may involve a greater incidence or severity of anemia-related symptoms, secondary to platinum therapy. Additionally, the more severe impact of a low Hb level may be related to the greater age of the gynecologic cancer patients and poorer health overall. Fatigue is a common symptom of anemia that diminishes energy and physical functioning, as well as mental capacity, emotional status, and overall QoL in cancer patients [14, 15]. Moreover, the presence of fatigue may add to the burden of both breast cancer and gynecologic cancer patients, who typically experience a host of other treatment- and disease-related problems that diminish physical reserves and function, such as, nausea, vomiting, pain, neurotoxicity, cachexia, and emotional distress [16]. In some patients, fatigue following chemotherapy may continue well beyond the end of treatment [17, 18]. Complaints of chemotherapy-related impaired cognitive function are becoming increasingly common, particularly among breast cancer patients receiving adjuvant chemotherapy. As with fatigue, the duration of treatment-related cognitive dysfunction can be prolonged, several reports citing evidence of this problem for 1–5 years after completion of chemotherapy [19–22]. The underlying cause of impaired cognitive function in patients receiving chemotherapy is unclear, but anemia development during chemotherapy, older age, change in hormonal status, and comorbidities (e.g., vascular disease, hypertension, diabetes) have been suggested as possible cofactors [23]. A recent study examined the relationships between Hb level and fatigue and cognitive function in cancer patients undergoing chemotherapy [24]. In that study, greater declines in Hb level were significantly (p <.05) related to greater increases in fatigue duration and disruptiveness and to worsening performance on three cognitive tasks in a subset of 49 patients whose Hb levels had declined to a final value of 12 g/dl or less [24]. These findings suggest that, in addition to a previously reported relationship with fatigue, declines in Hb during chemotherapy are associated with adverse changes in cognitive functioning.

In view of the relationships between low Hb (anemia), poor functional status, and other symptoms that can diminish patient QoL, correction of anemia appears to be a reason-able strategy for mitigating its adverse effects and potentially improving or preserving QoL. However, anemia has long been considered important enough to treat only if the patient developed serious organic symptoms [2, 25]. Unfortunately, despite evidence that even mild anemia can adversely affect QoL [26], many clinicians still hold this view, as demonstrated by the low anemia treatment rates seen in the ECAS. On the other hand, inroads regarding anemia treatment are being made, driven by a growing body of evidence indicating the merits of such treatment. Epoetin treatment has been shown in numerous studies to increase Hb level, decrease transfusion requirements, and improve QoL in anemic cancer patients with solid tumors and nonmyeloid hematologic malignancies [27–31]. Results of three prospective studies conducted specifically in patients with breast cancer or gynecologic cancer have shown similar results [32–34]. Also, retrospective subgroup analyses of data from studies of epoetin alfa administered three times weekly or once weekly have demonstrated a significant improvement in QoL of patients with breast cancer and gynecologic cancer [35–37]. Further, incremental analysis has shown that the most significant improvements in QoL occur when Hb level increases from 11 g/dl to 12 g/dl [38].

Analysis of the ECAS data has additionally provided a risk model for chemotherapy-induced anemia based on five factors identified as predictors of anemia. Clinical application of this model, which can identify patients as having a low, high, or highest risk of anemia, should improve anemia management by predicting which patients are most likely to become anemic during therapy, thereby allowing for earlier measures to effectively manage anemia and prevent anemia complications.

As shown here, the overall anemia risk model can be applied to breast and gynecologic cancer patients. However, while it has been shown that tumor type has a significant impact on the risk for developing anemia, modeling by individual tumor type could not be validated in the current data analysis. In breast and gynecologic cancer patients, of the five predictor variables (enrollment Hb level, tumor type [two options], platinum use, and gender), the enrollment Hb level and intent to use platinum are the best predictors of the development of anemia because breast cancer and gynecologic cancer patients are women.

In summary, given the known detrimental effects of anemia with respect to physical functioning and patient QoL, intervention before Hb values reach levels indicative of moderate or severe anemia or before patients develop clinical symptoms of anemia, irrespective of the Hb level, should be considered as part of the strategy for optimal management of patients with breast cancer and gynecologic cancer.

	APPENDIX

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The authors wish to thank the following ECAS participating centers:

Austria: A.ö. Krankenhaus der Barmherzigen Brüder Eisenstadt, Interne Abteilung, Eisenstadt; A.ö. Krankenhaus Waidhofen a.d. Thaya, Interne Abteilung, Waidhofen a.d. Thaya; A.ö. Krankenhaus der Stadt Linz, 1. Medizinsche Abteilung, Linz; A.ö. Krankenhaus der Barmherzigen Brüder St.Veit, Interne Abteilung, St.Veit; A.ö. Krankenhaus der Elisabethinen Linz, 1. Interne Abteilung, Linz; A.ö. Landeskrankenhaus Klagenfurt, 1. Medizinische Abteilung, Klagenfurt; A.ö. Landeskrankenhaus Steyr, 2. Medizinische Abteilung, Steyr; A.ö. Krankenhaus der Statutarstadt Wiener Neustadt, Chirurgische Abteilung, Wr. Neustadt; A.ö. Landeskrankenhaus Fürstenfeld, Medizinische Abteilung, Fürstenfeld; A.ö. Landeskrankenhaus Vöcklabruck, Abteilung für Innere Medizin, Vöcklabruck; A.ö. Krankenhaus Dornbirn, Interne Abteilung, Dornbirn; A.ö. Bezirkskrankenhaus Kufstein, Interne und Infektionsabteilung, Kufstein; Donauspital im SMZ-Ost der Stadt Wien, 2. Medizinische Abteilung, Vienna, Dr. Halbritter, Bad Vöslau; Hanusch-Krankenhaus, 3. Medizinische Abteilung, Vienna; Kaiserin-Elisabeth-Spital der Stadt Wien, Chirugische Abteilung, Vienna; Krankenanstalt der Stadt Wien Rudolfstiftung, 1. Medizinische Abteilung, Vienna; Krankenhaus der Stadt Wien Lainz, 5. Medizinische Abteilung, Vienna; Krankenhaus der Stadt Wien Lainz, Gynäkologisch-geburtshilfliche Abteilung, Vienna; Krankenhaus der Barmherzigen Schwestern Linz, HNO-Abteilung, Linz; Landeskrankenhaus Feldkirch, Abteilung für Innere Medizin, Feldkirch; Landeskrankenhaus Villach, Medizinische Abteilung mit Dialysestation, Villach; Sozialmedizinisches Zentrum Floridsdorf, Chirurgische Abteilung, Floridsdorf; St. Johanns Spital/LKH Salzburg, Landesklinik/Univ. Klinik f. Innere Medizin III, Salzburg; University Graz, Medizinische Univ. Klinik, Abteilung für Onkologie, Graz; University Graz, Medizinische Univ. Klinik, Abteilung für Hämatologie, Graz; University Graz, Geburtshilflich-Gynäkologische Univ. Klinik, Graz; University Innsbruck, Univ. Klinik für Innere Med., Klin. Abteilung für Hämatologie und Onkologie, Innsbruck; University Innsbruck, Univ. Klinik für Innere Med., Klin. Abteilung für Allgemeine Innere Medizin, Innsbruck; University Vienna, Univ. Klinik für Frauenheilkunde, Klinische Abteilung für Geburtshilfe und Frauenheilkunde, Vienna; University Vienna, Univ. Klinik für Frauenheilkunde, Klinische Abteilung für Spezielle Gynäkologie, Vienna; University Vienna, Univ. Klinik für Innere Medizin I, Vienna; Waldviertelklinikum Standort Horn, Abteilung für Innere Medizin, Horn; Weinviertelklinikum Schwerpunktkrankenhaus Mistelbach, II. Med. Abteilung, Mistelbach; Wilhelminenspital der Stadt Wien, 1. Medizinische Abteilung, Vienna; Wilhelminenspital der Stadt Wien, Gynäkolog. geburtshilfliche Abteilung, Vienna; Zentralklinikum St. Pölten, 1. Medizinische Abteilung, St. Pölten. Belgium: A.Z. Groeninge (Maria’s Voorzienigheid), Kortrijk; A.Z. Jan Palfijn – Gallifort (J. Palfijn), Merksem; A.Z. M. Middel. – St.-Jozef (M. Middel.), Gent; A.Z. St. – Jan a.v. Brugge; Academisch Ziekenhuis VUB, Jette; Alg. Centrumzkh Antwerpen (Stuivenberg), Antwerpen; AZ Middelheim, Antwerpen; C.H. de l’Ardenne (Libramont), Libramont; C.H. Hutois, Huy; C.H. Jolimont – Lobbes (Jolimont), Haine-St-Paul; C.H. Peltzer – La Tourelle (Tourelle), Verviers; C.H.R. Citadelle (Citadelle), Liège; C.H.R. de Tournai (La Dorcas), Tournai; C.H.R. St.- Joseph – Warquignies (St-Jos), Mons; C.H.U. de Charleroi (Vésale), Montigny-le-Tilleul; C.H.U. Sart-Tilman, Liège; C.H.U. Tivoli La, Louvière; Centre Hospitalier Luxembourg, Luxembourg; Clin. Univ. Bruxelles Hôpital Erasme, Anderlecht; Clinique Notre Dame, Tournai; Clinique St.- Pierre, Ottignies; Clinique Ste-Anne – St.-Rémi, Anderlecht; Clinique Ste-Elisabeth, Luxembourg; Clinique Ste- Elisabeth, Namur; Cliniques de l’Europe (Ste-Elisabeth), Uccle; Cliniques Universitaires St.-Luc, Woluwe-St-Lambert; Institut Jules Bordet, Bruxelles; R.H.M.S. (Baudour), Baudour; Regionaal Ziekenhuis Sint-Maria vzw, Halle; UZ Antwerpen, Edegem; UZ Gasthuisberg, Leuven; UZ Gent, Gent; Ziekenhuis Henri Serruys, Oostende. Czech Republic: Bata Hospital, Oncology Dept; Charles University Hospital, Praha, 1st Internal Dept; Charles University Hospital, Praha, Oncology Dept; Hospital eske Budejovice, Radiation Oncology Dept; Hospital Chomutov, Oncology and Radiotherapy Dept; Hospital Jihlava, Radiotherapy Dept; Hospital Liberec, Radiation and Clinical Oncology Dept; Hospital Prerov, Oncology Outpatient Dept; Hospital Sumperk, Oncology Outpatient Dept; Hospital Znojmo, Radiation and Clinical Oncology Dept; Masaryk Hospital, Usti nad Labem, Radiotherapy Dept; Masaryk Oncology Institute, Brno; St. Anne’s University Hospital, Brno, Radiation Oncology Dept; Thomayer University Hospital, Praha, Oncology Dept; University Hospital Hradec Kralove, Radiation Oncology Dept; University Hospital Kralovske Vinohrady, Praha, Haematology Dept; University Hospital Kralovske Vinohrady, Praha, Radiotherapy and Oncology Dept; University Hospital Motol, Praha, Clinical and Radiation Oncology Dept; University Hospital Na Bulovce, Praha, Radiation Oncology Institute; University Hospital Olomouc, Oncology Dept; University Hospital Ostrava, Clinical Haematology Dept; University Hospital Ostrava, Radiotherapy and Oncology Dept; University Hospital Plzen, Haematology Dept; University Hospital Plzen, Radiotherapy and Oncology Dept. Estonia: Tartu University, Tartu, Hemato-Oncology Clinic. Finland: Helsinki University Hospital, Helsinki; Satakunta Central Hospital, Pori; Tampere University Hospital, Tampere; Turku Univesity Hospital, Turku. France: Centre Hospitalier André Mignot, Le Chesnay; Hôpital Avicenne, Bobigny; Institut Bergonié, Bordeaux; Centre Antoine Lacassagne, Nice; Centre Hospitalier Spécialisé en Pneumologie, Chevilly Larue; Centre d De Radiothérapie Privé, Béeziers; Centre du Rouget, Sarcelles; Centre Hospitalier, Beauvais; Centre Hospitalier Bel-Air, Thionville; Centre Hospitalier, Belley; Centre Hospitalier Bligny, Bris Sur Forge; Centre Hospitalier Bon Secours, Metz; Centre Hospitalier Broussais, Saint- Malo; Centre Hospitalier Fontenoy, Chartres; Centre Hospitalier Gonesse, Gonesse; Centre Hospitalier Intercommunal De Créteil, Créteil; Centre Hospitalier Intercommunal Le Raincy, Montfermeil; Centre Hospitalier Lyon Sud, Lyon; Centre Hospitalier Manchester, Charleville Méezieres; Centre Hospitalier Mantes La Jolie, Mantes La Jolie; Centre Hospitalier, Niort; Centre Hospitalier, Romans; Centre Hospitalier Saint-Vincent, Lille; Centre Hospitalier Tourcoing,Tourcoing; Centre Jean Perrin, Clermont-Ferrand; Centre Hospitalier, d’Angoulême; CH Car remeau, Nîmes; CH Gaston Doumergue, Nîmes; CHG, Perpignan; CHG A. Boulloche, Montbéeliard; CHG Bourg-En-Bresse; CHG Brive-La-Gaillarde; CHG Châlon, Châalon- Sur-Saôone; CHG Chambéery; CHG De Valenciennes, Valenciennes; CHG François Mitterand, Pau; CHG J. Monnet, Epinal; CHG Jacques Monodean Mermozj, Montivilliers; CHG Libourne; CHG, Moulins; CHG, Valence; CHR Purpan, Toulouse; CHRU Bocage, Dijon; CHRU Gabriel Montpied, Clermont-Ferrand; CHRU Hôtel Dieu, Clermont-Ferrand; CHS, Sarrebourg; CHU Angers; CHU Archet, Nice; CHU Arnaud De Villeneuve, Montpellier; CHU, Avignon; CHU Brabois Adultes, Vandoeuvre Les Nancy; CHU Huriez, Lille; CHU J. Minjoz, Besancon; CHU Lapeyronie, Montpellier; CHU Michallon, Grenoble; CHU Morvan, Brest; CHU, Poitiers; CHU Pontchaillou, Rennes; CHU Rangueil, Toulouse; CHU Rouen; CHU Saint André, Bordeaux; CLCC A.Vautrin, Vandoeuvre Les Nancy; CLCC Becquerel, Rouen; CLCC Bergonié, Bordeaux; CLCC E. Marquis, Rennes; CLCC Val d’Aurelle, Montpellier; Clinique Alleray-Labrouste, Paris 15è; Clinique Beauregard, Marseille; Clinique C.Bernard, Metz; Clinique Chirurgicale, Chatou; Clinique Des Dentellières, Valenciennes; Clinique Des Dômes, Clermont-Ferrand; Clinique DREVON, Dijon; Clinique Du Mail, Amiens; Clinique Du Parc, Cholet; Clinique Du Pont De Chaume, Montauban; Clinique Gentilly, Nancy; Clinique Hartmann, Neuilly; Clinique des Ormeaux, Le Havre; Clinique, Rouen; Clinique Saint François, Mainvilliers; Clinique Saint Jean Languedoc, Toulouse; Clinique Saint Jean, Lyon; Clinique Saint Pierre, Perpignan; Clinique Saint Vincent, Besancon; Clinique Sainte-Anne, Langon; CHG, Perigueux; Clinique Tivoli, Bordeaux; HIA Desgenettes, Lyon; HIA Percy, Clamart; Hôpital Ambroise Paré, Boulogne; Hôpital Anglais, Levallois Perret; Hôpital Béclère, Clamart; Hôpital Cochin, Paris 14è; Hôpital De Lagny, Lagny; Hôpital De Pontoise, Pontoise; Hôpital Des Peupliers, Paris 13è; Hôpital Du Val De Grâace, Paris; Hôpital Européen Georges Pompidou, Paris; Hôpital Font- Pré, Toulon; Hôpital, Freyming Merlenbach; Hôpital Les Chânaux, Mâacon; Hôpital Maillot, Briey; Hôpital Militaire Laveran, Marseille; Hôpital Pasteur, Nice; Hôpital Poissy, Poissy; Hôpital Privé Des Yvelines, Sartrouville; Hôpital Rebeyrol, Limoges; Hôpital Robert Boulin, Libourne; Hôpital Saint- Joseph, Marseille; Hôpital Sainte- Marguerite, Marseille; Hôpital La Timone, Marseille; HPD Perpétuel Ssecours, Levallois; Institut Claudius Regaud, Toulouse; Institut Jean Godinot, Reims; Institut Paoli Calmette, Marseille; CHU La Pitié Salpétrière, Paris 13è; Maison Médicale Marzet, Pau; Hôpital Paul Brousse, Villejuif; Pierre Bénite, Lyon; Polyclinique Saint-Côme, Compiegne; Hôpital Tenon, Paris; CH, Niort; Centre Hospitalier Sud Francilien, Corbeil Essonnes. Germany: Evangelisches Krankenhaus, Holzminden; Friedrich Ebert Krankenhaus, Neumünster; Gemeinnützige Ökumenische Krankenhausgesellschaft Ibbenbüren, Ibbenbüren; Gemeinschaftspraxis Dr. Schmitz/Dr. Steinmetz, Köln; Kliniken St. Antonius gem. GmbH, Wuppertal; Klinikum Augsburg, Augsburg; Klinikum Mannheim, Mannheim; Klinikum Neukölln, Berlin; Knappschaftskrankenhaus Dortmund, Dortmund; LMU-München-Innenstadt, München; Praxis Dr. Buschmann, Bonn; Praxis Dr. Kirschner, Solingen; Praxis Dr. Seibt-Jung, Berlin; Praxis Dr. Semsek, Freiburg; Praxis Dr. Tsamaloukas, Hilden; Praxis Professor Rohrberg, Halle; RWTH, Aachen; St. Marien- Hospital, Hamm; Städt. Kliniken Oldenburg, Oldenburg; Theresienhospital Mannheim, Mannheim; Uniklinik Heidelberg, Heidelberg; Universität Rostock, Rostock; Universität Tübingen, Tübingen; Universitätskliniken des Saarlandes, Homburg; Universitätsklinikum Benjamin Franklin, Berlin. Greece: Panagia-2nd IKA Hospital, Thessaloniki; G. Gennimatas-6th IKA Hospital, Athens; A.H.E.P.A. University Hospital, Thessaloniki; Alexandra General Hospital, Athens; Aretaieio University Hospital, Athens; Evangelismos General Hospital, Athens; G. Gennimatas General Hospital, Athens; University General Hospital of Alexandroupolis, Alexandroupolis; G. Papanikolaou General Hospital, Thessaloniki; University General Hospital of Ioannina, Ioannina; General Hospital of Larisa, Larisa; General Hospital of Kavala, Kavala; University General Hospital of Patras, Patras; Hygeia Diagnostic & Theraupeutic Center, Athens; Athens Medical Center, Athens; Ippokratio General Hospital, Athens; Ippokratio General Hospital, Thessaloniki; Laiko General Hospital, Athens; Elenas Venizelou General Maternity Hospital, Athens; Metaxa Anticancer Hospital, Piraeus; Papageorgiou General Hospital, Thessaloniki; University General Hospital of Heraklion, Crete; Sismanoglio General Hospital, Athens; Sotiria General Hospital, Athens; Agioi Anargyroi Kifissias Anticancer Hospital, Athens; Agios Savvas Anticancer Hospital, Athens; Theagenio Anticancer Hospital, Thessaloniki; Agios Andreas General Hospital, Patras; General Hospital of Kalamatas, Kalamatas; Andreas Papandreou General Hospital, Rhodes; 424 General Military Hospital, Thessaloniki; Elpis General Hospital, Athens; Venizelio General Hospital of Heraklion, Crete; Evgenidio Therapeutic Center, Athens. Hungary: National Institute of Oncology, Budapest; Pest Megyei Tüdgyógyintézet, Törökbálint; Semmelweis University of Medicine, Budapest; Szent Imre Kórház, Budapest; Uzsoki Utcai Kórház, Budapest. Italy: A.O. A. Di Summa U.O. Radioterapia, Brindisi; A.O. Bianchi Melacrino Morelli U.O. Radioterapia, Reggio Calabria; A.O. Bianchi Melacrino Morelli Ematologia, Reggio Calabria; A.O. C. Poma U.O. Radioterapia, Mantova; A.O. Careggi U.O. Ematologia, Firenze; A.O. Careggi U.O. Radioterapia Ospedaliera e Universitaria, Firenze; A.O. di Padova (Policlinico) Immunologia Clinica, Padova; A.O. di Padova U.O. Radioterapia, Padova; A.O. Istituti Ospitalieri U.O. Radioterapia, Cremona; A.O. Maggiore della Carità U.O. Radioterapia, Novara; A.O. Ospedale Civile Mariano Santo U.O. Radioterapia, Cosenza; A.O. Ospedale di Circolo Macchi U.O. Radioterapia, Varese; A.O. Ospedale di Circolo U.O. Radioterapia, Busto Arsizio; A.O. Ospedale Ferrarotto Divisione Ematologia, Catania; A.O. Ospedale Maggiore di Trieste II Divisione Medica/Ematologia, Trieste; A.O. Ospedale Maggiore di Trieste U.O. Radioterapia, Trieste; A.O. Ospedale Niguarda Ca’ Granda, Milano; A.O. Ospedale Policlinico Universitario di Udine Clinica Ematologica, Udine; A.O. Pisana Spedali Riuniti S.Chiara Ematologia, Pisa; A.O. Pisana Spedali Riuniti S.Chiara U.O. Radioterapia; A.O. Policlinico Consorziale U.O. Radioterapia, Bari; A.O. Policlinico Consorziale Univ. Ematologia I, Bari; A.O. Policlinico Monteluce Sez. Immunologia Clinica, Perugia; A.O. Policlinico Monteluce U.O. Radioterapia, Perugia; A.O. Policlinico Universitario G. Martino U.O. Radioterapia, Messina; A.O. S Antonio Abate Divisione Ematologia, Gallarate; A.O. S Gerardo dei Tintori Divisione Ematologia, Monza; A.O. S Gerardo dei Tintori U.O. Radioterapia, Monza; A.O. S Giovanni Battista Divisione Ospedaliera Ematologia, Torino; A.O. S Giovanni Battista Divisione Universitaria Ematologia, Torino; A.O. S Giovanni Battista U.O. Radioterapia Dir. Universitaria, Torino; A.O. S Giuseppe Moscati Divisione Ematologia, Avellino; A.O. S Maria della Misericordia U.O. Radioterapia, Udine; A.O. Spedali Civili di Brescia U.O.Radioterapia, Brescia; A.O. SS. Annunziata Divisione Ematologia, Taranto; A.O. Umberto I Clinica di Ematologia, Ancona; C.R.O Aviano U.O. Radioterapia, Aviano; Casa di Cura S Pio X Divisione Radioterapia, Milano; Divisione Ematologia, Reggio Calabria; Fondazione S. Maugeri U.O. Radioterapia, Pavia; A.O. S.Luigi Gonzaga Direzione Universitaria Medicina Interna II, Orbassano; IFO Istituto Regina Elena Divisione Ematologia, Roma; IFO Istituto Regina Elena U.O. Radioterapia, Roma; Istituto Clinico Humanitas Divisione Oncologia Medica e Ematologia, Rozzano (MI); Istituto Nazionale Tumori U.O. Radioterapia B, Milano; Istituto Policlinico S. Donato U.O. Radioterapia, S. Donato Milanese (MI); O. A. Di Summa Divisione Ematologia, Brindisi; Ospedale Civico Montefiascone U.O. Ematologia, Montefiascone (VT); Ospedale Civico S. Croce Divisione Ematologia, Cuneo; Ospedale Civile D.H. Ematologia, Sestri Levante (GE); Ospedale Civile Divisione Ematologia, Legnano; Ospedale Civile Divisione Ematologia, Matera; Ospedale Civile S.Timoteo SIT Onco-Ematologico, Termoli; Ospedale Civile Umberto I Divisione Ematologia, Venezia- Mestre; Ospedale Degli Infermi Rimini Divisione Ematologia, Rimini; Ospedale Degli Infermi U.O. Radioterapia, Biella; Ospedale di Circolo A. Manzoni U.O. Radioterapia, Lecco; Ospedale di Vicenza Divisione Ematologia, Vicenza; Ospedale di Vicenza U.O. Radioterapia, Vicenza; Ospedale La Maddalena Divisione Ematologia, Palermo; Ospedale Maggiore I.R.C.C.S. Centro TMO, Milano; Ospedale Maggiore I.R.C.C.S. Divisione Ematologia, Milano; Ospedale Mauriziano U.O. Radioterapia, Torino; Ospedale Oncologico U.O. Radioterapia, Rionero in Vulture (PZ); Ospedale P. Calvi Divisione Onco-Ematologia, Noale (VE); Ospedale Regionale Divisione Ematologia, Bolzano; Ospedale S. Anna U.O. Radioterapia, Ferrara; Ospedale S. Giovanni Vecchio U.O. Radioterapia, Torino; Ospedale S. Maria Goretti U.O. Ematologia, Latina; Ospedale S. Martino Clinica di Ematologia DIMI, Genova; Ospedale S. Martino Ematologia Ambul.e D.H., Genova; Ospedale S. Martino Ematologia II e Centro TMO, Genova; Ospedale S. Raffaele Centro trasfusionale SIMIT, Milano; Ospedale San Giacomo in Augusta Day Hospital Ematologia, Roma; Ospedale San Giovanni Divisione Ematologia, Roma; Ospedale San Giovanni U.O. Radioterapia, Roma; Ospedale San Pietro - Fatebenefratelli U.O. Radioterapia, Roma; Ospedale San Salvatore U.O. Ematologia e TMO, Pesaro; Ospedale Sant’Eugenio Cattedra Ematologia, Roma; Ospedale. S.S. Antonio e Biagio Divisione Ematologia Sezione Universitaria, Alessandria; OspedaleCervello Divisione Ematologia, Palermo; Ospedali Riuniti U.O. Radioterapia, Bergamo; Policlinico S. Matteo Istituto di Ematologia, Pavia; Policlinico S. Orsola Malpighi U.O. Radioterapia, Bologna; Policlinico S.Orsola Malpighi Divisione Ematologia, Bologna; Policlinico Universitario Gemelli Divisione Ematologia, Roma; Policlinico Universitario Gemelli U.O. Radioterapia, Roma; Presidio Ospedaliero Umberto I Divisione Ematologia, Frosinone; Unità Operativa Ematologia Oncologica Emon, Napoli; Universitarie Divisione Ematologia, Sassari. Latvia: Radiation and Chemotherapy Center, P. Stradins University Hospital, Riga; State Haematology Center, Riga; State Oncology Center, Riga. Lithuania: Kaunas Medical University Oncology Clinic, Kaunas; Kaunas Oncology Hospital, Kaunas; Klaipeda Hospital Oncology Department, Klaipeda; Lithuanian Oncology Center, Vilnius; Panevezys Hospital, Department of Chemotherapy, Panevezys; Siauliai Hospital, Oncology Department, Siauliai. Norway: Det Norske Radiumhopital, Academic Center, Department of Gynecology; Haukeland Sykehus, Community Center, Department of Gynecology; Regionsykehuset i Trondheim, Community Center, Department of Oncology; Sentralsykehuset i Vestfold, Community Center, Department of Oncology. Netherlands: Academisch Medisch Centrum, Amsterdam; Academisch Ziekenhuis Maastricht, Maastricht; Albert Schweitzer Ziekenhuis, Dordrecht; Amphia Ziekenhuis, Breda; Anthonius Ziekenhuis, Sneek; Atrium Medisch Centrum, Heerlen; Catharina Ziekenhuis, Eindhoven; Diakonessenhuis, Utrecht; Flevo Ziekenhuis, Almere; Fransiscus Ziekenhuis, Roosendaal; Gelre Ziekenhuizen, Apeldoorn; Gelre Ziekenhuizen, Zutphen; Groene Hart Ziekenhuis, Gouda; Ijsselmeer Ziekenhuizen, Emmeloord; Ikazia Ziekenhuis, Rotterdam; Isala Klinieken, Zwolle; Jeroen Bosch Ziekenhuis, Den Bosch; Leids Universitair Medisch Centrum, Leiden; Maxima Medisch Centrum, Veldhoven; Medisch Centrum Rijnmond Zuid, Rotterdam; Medisch Spectrum Twente, Enschede; Onze Lieve Vrouwe Gasthuis, Amsterdam; Oosterschelde Ziekenhuis, Goes; Refaja Ziekenhuis, Stadskanaal; Sint Lucas Ziekenhuis, Winschoten; Spaarne Ziekenhuis, Haarlem; St. Anna Zorgstichting, Geldrop; VieCuri Medisch Centrum voor Noord Limburg, lokatie St. Maartens Gasthuis, Venlo; Streekziekenhuis de Honte, Terneuzen; Streekziekenhuis Midden-Twente, Hengelo; Streekziekenhuis Zevenaar, Zevenaar; Vlietland Ziekenhuis, Schiedam; Vlietland Ziekenhuis, Vlaardingen; Wilhelmina Ziekenhuis, Assen; Ziekenhuis Bethesda, Hoogeveen; Ziekenhuis Coevoorden-Hardenberg, Hardenberg; Ziekenhuis de Heel, Zaandam; Ziekenhuis De Tjongerschans, Heerenveen; Ziekenhuis Gelderse Vallei, Ede; Ziekenhuis Gelderse Vallei, Zutphen Ziekenhuis Leyenburg, Den Haag; Ziekenhuis Lievensberg, Bergen op Zoom; Ziekenhuis Rijnstate, Arnhem; Ziekenhuis St. Jansdal, Harderwijk; Ziekenhuis Walcheren, Vlissingen. Poland: Akademia Medyczna – Oddz. Onkologii I Radioter., Gdask; Klinika Chemioterapii, Instytut Onkologii, Gliwice; Kilnika Chemioterapii, Instytut Onkologii, Kraków; Klinika Nowotworów Puca i Klatki Piersiowej, Centrum Onkologii – Instytut, Warszawa; Klinika Nowotworów Ukadu Chonnego, Centrum Onkologii – Instytut, Warszawa; Klinika Onkologii Ginekologicznej Pozna, Pozna; Klinika Onkologii, Oddz. Kobiecy, CSK WAM, Warszawa; Klinika Onkologii, Oddz. Mski, CSK WAM, Warszawa; Klinika Onkologii PSK1 Pozna, Pozna; Klinika Radioterapii, Instytut Onkologii, Gliwice; Lubuski Orodek Onkologiczny, Zielona Góra; Oddz. Chemioterapii DCO Wrocaw, Wrocaw; Oddz. Chemioterapii RCO Bydgoszcz, Bydgoszcz; Oddz. Radioterapii I DCO Wrocaw, Wrocaw; Oddz. Radioterapii II DCO Wrocaw, Wrocaw; Oddz. Radioterapii III DCO Wrocaw, Wrocaw; Oddz. Radioterapii WCO Pozna, Pozna; Oddz. Radioterapii – Por. WCO Pozna, Pozna; Oddz.Ginekol. Onkol. WCO Pozna, Pozna; Oddzia Ginekologii Onkol., Regionalny Orodek Onkologiczny, ód; Regionalny Szpital Onkologiczny-Radioterapia, Szczecin; Regionalny Szpital Onkologiczny-Radioterapia, Szczecin; Szpital Morski im. PCK-oddz. Radioterapii, Gdask; Szpital Morski im. PCK-oddz. Radioterapii, Gdynia; Szpital Wojewódzki- oddzia Chemioterapii, Elblág; Szpital, Oddz. Onkologii, Pleszew; Wielkopolskie Centrum Chorób Puc I Grulicy, Pozna; Wojewódzki Szpital Zesp.-Oddz. Chemioterapii, Toru; Zakad Onkologii AM, Biaystok; Zakad Teleradioterapii, Centrum Onkologii – Instytut, Warszawa. Portugal: Centro Hosp. V. N. Gaia, V.N.Gaia; Centro Hospitalar Coimbra., Coimbra; H. Barlavento Algarvio, Portimão; Hosp. Distr. Beja, Beja; Hosp. Distr. Faro, Faro; Hosp. Égas Moniz, Lisboa; Hosp. Espirito Santo, Évora; Hosp. Inf. D. Pedro, Aveiro; Hosp. Joaquim Urbano, Porto; Hosp. Militar Porto, Porto; Hosp. Pulido Valente, Lisboa; Hosp. S. Bernardo, Setúbal; Hosp. S. Sebastião, S.M. Feira; Hosp. Sta. Maria, Lisboa; Hosp. Universidade Coimbra, Coimbra; IPO-Lisboa, Lisboa; IPO-Porto, Porto. Romania: Oncological Institute of Bucharest, Bucharest; Oncological Institute of Cluj, Cluj. Russia: Central Clinical Hospital; Moscow Regional Oncology Dispensary; Russian Cancer Research Center. Slovak Republic: Ambulancia klin. onkológie, Rim. Sobota; FNsP L. Pasteura, Koice; MFN, Onkologické odd., Martin; NOÚ, Interné odd., Bratislava; NOÚ, Iodd. Ambulantnej CHT, Bratislava; NsP Bardejov; NsP FDR, Onkologické oddelenie, B. Bystrica; NsP Odd. RT a CHT, Nitra; NsP Odd. RT a CHT, ilina; NsP Onkol. klinika, Trnava; NsP Onkologické odd., Humenné; NsP Onkologické odd., Poprad; NsP Onkologické odd., Preov; NsP Onkologické odd., Trebiov; NsP Onkologické odd., Trenín; NsP POKO, 000Luenec; NsP POKO, Doln Kubín; NsP POKO, Galanta; NsP POKO, Piet’any; NsP POKO, Skalica; NsP . Kukuru, Onkologické odd., Michalovce; OÚSvA, Klinika onkológie a rádioterapie, Bratislava; Ústav TBC a RCH, Onkol. oddelenie, Nitra- Zobor; Ústav TBC a RCH, Pneumo-onkologické odd., Bratislava. Slovenia: General hospital Maribor; Oncology institute of Ljubljana. Spain: Hosp. Ntra. Sra. de Aranzazu, Bilbao; Hosp. Carlos Haya, Málaga; Hosp. Central de Asturias, Oviedo; Hosp. Ciudad de Jaen, Jaen; Hosp. Clinic i provincial Barcelona, Barcelona; Hosp. Clinico Salamanca; Hosp. Clinico Univ. San Carlos, Madrid; Hosp. Clinico Univ. de Zaragoza; Hosp. Comarcal del Bierzo, Leon; Hosp. Cruces, Bilbao; Hosp. de Castellón, Castellon; Hosp. Gral. Univ. Gregorio Marañón, Madrid; Hosp. Materno Infantil, Málaga; Hosp. Central de la Defensa, Madrid; Hosp. Montecelo, A Coruña; Hosp. Sant Pau, Barcelona; Hosp. Esperança, Barcelona; Hosp. Torrecárdenas, Almería; Hosp. Univ. 12 de Octubre, Madrid; Hosp. Univ. Candelaria, Tenerife; Hosp. Univ. Germa Trias y Pujol, Badalona; Hosp. Univ. La Fe, Valencia; Hosp. Clinico Univ. Valladolid; Hosp. Univ. La Paz, Madrid; Hosp. Univ. La Princesa, Madrid; Hosp. Univ. Puerta de Hierro, Madrid; Hosp. Univ. Puerta del Mar, Cadiz; Hosp. Univ. Ramon y Cajal, Madrid; Hosp. Univ. Reina Sofia, Cordoba; Hosp. Univ. Vall d’Hebrón, Barcelona; Hosp. Univ. Virgen de las Nieves, Granada; Hosp. Univ. Virgen del Rocío, Sevilla; Hosp. Univ. Virgen Arrixaca, Murcia; Hosp. Univ. Marqués de Valdecilla, Santander; Hosp. Virgen Macarena, Sevilla; Instituto Catalan de Oncología (ICO), Barcelona; Instituto Valenciano de Oncología (IVO), Valencia. Sweden: Akademiska Sjukhuset, Uppsala; Borås Lasarett, Borås; Centrallasarettet, Västerås; Centralsjukhuset, Karlstad; Falu Lasarett, Falun; Helsingborgs Lasarett, Helsingborg; Länssjukhuset Gävle-Sandviken, Gävle; Länssjukhuset Ryhov, Jönköping; Länssjukhuset, Sundsvall; Mälarsjukhuset, Eskilstuna; Norrlands Universitetssjukhus, Umeå; Radiumhemmet, Stockholm; Regionsjukhuset, Örebro; Sahlgrenska Sjukhuset, Göteborg; Södersjukhuset; Universitetssjukhuset, Linköping; Universitetssjukhuset, Lund; Växjö Centrallasarett, Växjö. Switzerland: CHUV, Lausanne, Med. Oncology; Clinique de Carouge, Med. Oncology; Clinique de Genolier, Med. Oncology and Radio- Oncology; Hôpital de la Gruyère, Riaz, Med. Oncology; Hôpital de la Providence, Vevey, Med. Oncology; Hôpital de la Ville, Neuchâtel, Med. Oncology; Inselspital Bern, Radio-Oncology; Kantonsspital Basel, Med. Oncology and Radio-Oncology; Kantonsspital Luzern, Radio-Oncology; Kantonsspital St. Gallen, Radio-Oncology; Kantonsspital Winterthur, Radio-Oncology; Lindenhofspital Bern, Radio-Oncology; Praxis Dr. Mannhart, Baar; Praxis Dr. Michel-Reymond, Lausanne; Praxis Dr. Paschoud, Lausanne; Praxis Dr. Tran-Thang, Lausanne; Praxis Dr. Zoppi, Bern; Praxis Frau Dr. Hasler, Biel; Praxis Herr Dr. Cech, Lausanne; Praxis Herr Dr. Gattiker, Zürich; Praxis Herr Dr. von Fliedner, Pully; Spital Thun, Med. Oncology; St. Claraspital Basel, Med. Oncology; Universitätsspital Zürich, Radio-Oncology; ZETUP, St. Gallen, Med. Oncology. United Kingdom: Aberdeen Royal Infirmary, Aberdeen; Addenbrooke’s NHS Trust, Cambridge; Barnsley District Hospital; Beaston Oncology Centre, Glasgow; Bedford Hospital; Belvior Park Hospital, Belfast; Bristol Haematology & Oncology Centre, Bristol; Bronglais General Hospital, Wales; Charing Cross Hospital, London; Cheltenham General Hospital; Christie Hospital, Manchester; Cork University Hospital; Cromwell Hospital, London; Essex Rivers NHS Trust; Freeman Hospital, Newcastle Upon Tyne; Glan Clywd Hospital, Wales; Guy’s Hospital, London; Hammersmith Hospital, London; Hinchingbrooke Healthcare NHS Trust; Inverclyde Royal Hospital, Greenock; Ipswich Hospital NHS Trust; James Cook Unversity Hospital, Middlesborough; James Paget Healthcare NHS Trust; Jersey General Hospital; John Radcliffe Hospital, Oxford; Mid Western Regional Hospital, Ireland; Norfolk & Norwich University Hospital NHS Trust; Princess Alexandra Hospital, Harlow; Princess Royal Hospital, Hull; Queen Elizabeth Hospital NHS Trust, Kings Lynn; Royal Hallamshire Hospital, Sheffield; Royal Preston Hospital; Royal Shrewsbury Hospital; Royal South Hants Hospital; Royal Sussex County Hospital; Singleton Hospital, Wales; St. Georges Hospital, London; Stobhill General Hospital, Glasgow; Swansea NHS Trust; Ulster Hospital, Belfast; University College Hospital, Galway; University College London; University Hospital of Wales; Velindre NHS Trust, Cardiff; Walsgrave Hospitals NHS Trust; West Suffolk Hospital; West Wales General Hospital; Weston General Hospital, Bristol; Weston Park Hospital, Sheffield; Withybush Hospital, Haverfordwest; Wythenshawe Hospital, Manchester.

	DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

Top Learning objectives Abstract Introduction Materials and methods Results Discussion Appendix Disclosure of potential... References

 
Dr. Schrijvers has acted as a consultant for Ortho Biotech. Dr. Bokemeyer has acted as a consultant for Amgen, Ortho Biotech, and Roche.

	REFERENCES

Top Learning objectives Abstract Introduction Materials and methods Results Discussion Appendix Disclosure of potential... References

 

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