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BACKGROUND: The total burden of melanoma has already been studied but little is known about the distribution of this burden amongst localised, node metastatic and distant metastatic stages. METHODS: Disability-adjusted life years (DALY) assesses disease burden, being the sum of years of life with disability (YLD) and years of life lost (YLL). A melanoma disease model was developed in order to predict the evolution of patients from diagnosis until death. The model was applied to a large cohort of 8016 melanoma patients recorded by the Belgian Cancer Registry for incidence years 2009-2011. DALYs were calculated for each American Joint Committee on Cancer stage, considering stage at diagnosis on the one hand and time spent in localised, node metastatic and visceral metastatic stages on the other. Probabilistic sensitivity analyses and scenario analyses were performed to explore uncertainty. FINDINGS: Our analyses resulted in 3.67 DALYs per melanoma, 90.81 per 100,000 inhabitants, or 32.67 per death due to melanoma. The total YLL accounted for 80.4% of the total DALY. Stages I, II, III and IV patients at diagnosis generated, respectively, 27.8%, 32.7%, 26.2% and 13.3% of the total YLL. For the time spent in each stage, localised melanomas, node metastatic melanomas, and distant metastatic accounted, respectively, for 34.8%, 52.6% and 12.6% of the total YLD. Parametric uncertainty was very limited, but the influence of using pre-2010 Global Burden of Disease approaches was substantial. INTERPRETATION: The total DALY for melanoma was consistent with the previous studies. Our results in terms of proportions of DALY/YLL/YLD per stage could be extrapolated to other high-income countries. YLDs generated by localised melanoma which will never metastasize were inferior to YLLs resulting from stage IA melanomas. This result supports the hypothesis that efforts for an earlier diagnosis of melanoma are important. FUNDING: None.

17 p., ill, On sait aujourd’hui avec certitude qu’il existe un lien de cause à effet entre le cancer du col de l’utérus et la présence du papillomavirus (HPV), transmis par voie sexuelle. Le KCE (Centre Fédéral d’Expertise des Soins de Santé) a établi, en collaboration avec l’Institut scientifique de Santé Publique et le Registre du Cancer, qu’un dépistage basé sur la détection de la présence du virus serait plus efficace que l’actuel frottis (aussi appelé Pap-test) pour protéger les femmes de plus de 30 ans, et ceci à un coût moins élevé. De plus, le dépistage par test HPV permettrait en toute sécurité d’espacer les examens de 5 ans au lieu de 3 ans aujourd’hui. Il reste cependant important que toutes les femmes entre 25 et 64 ans, y compris celles qui sont vaccinées contre ce virus, continuent à se faire dépister. En effet, le vaccin ne protège pas contre tous les types de virus HPV pouvant générer un cancer, et on ne connaît pas encore avec certitude la durée de la protection qu’il confère., PRÉFACE 2 -- QUESTIONS DE RECHERCHE 3 -- MESSAGES CLÉS. 3 -- CONTEXTE 4 -- RÉSULTATS 6 -- 1. LE TEST HPV EST PLUS SENSIBLE QUE LE PAP-TEST POUR LA DÉTECTION DES LÉSIONS PRÉCANCÉREUSES CIN2 ET CIN3. PAR CONTRE, SA SPÉCIFICITÉ EST MOINDRE 6 -- 2. L’EFFET PROTECTEUR DU TEST HPV VIS-À-VIS DES CANCERS INVASIFS EST CLAIREMENT SUPÉRIEUR À CELUI DU PAP-TEST, D’APRÈS LES RÉSULTATS D’ÉTUDES CLINIQUES RANDOMISÉES. CET AVANTAGE N’EST PAS DÉMONTRÉ EN DESSOUS DE L’ÂGE DE 30 ANS. 7 -- 3. L’INTERVALLE DE DÉPISTAGE PEUT ÊTRE AUGMENTÉ EN TOUTE SÉCURITÉ JUSQU’À 5 ANS, VOIRE PLUS, AVEC LE TEST HPV. 8 -- 4. L’ALGORITHME RECOMMANDÉ POUR UN DÉPISTAGE ORGANISÉ EST UNE STRATÉGIE DE TRIAGE EN DEUX ÉTAPES, AVEC LE TEST HPV COMME EXAMEN PRIMAIRE, ET AVEC DEUX PAP-TESTS EN CAS DE RÉSULTAT ASC-US OU GRADE PLUS ÉLEVÉ 8 -- 5. TESTS CYTOLOGIQUES : IL N’EXISTE PAS DE CONTRÔLE DE QUALITÉ POUR LEUR INTERPRÉTATION. 9 -- 6. TESTS HPV : L’ACCRÉDITATION ISO15189 EST OBLIGATOIRE POUR LEUR REMBOURSEMENT, MAIS LE DISPOSITIF N’EST PAS ENCORE ENTIÈREMENT EN PLACE. 10 -- 7. LE DÉPISTAGE ACTUEL MANQUE D’EFFICIENCE : TROP PEU DE FEMMES SONT DÉPISTÉES MAIS À UNE FRÉQUENCE TROP ÉLEVÉE. L’USAGE DE LA COLPOSCOPIE EST EXCESSIF. 10 -- 8. LA PROPORTION DE RÉSULTATS ANORMAUX DES TESTS CYTOLOGIQUES EST TRÈS VARIABLE D’UN LABORATOIRE À L’AUTRE 12 -- 9. IL EST PEU PROBABLE QUE L’INTRODUCTION DU DÉPISTAGE PAR TEST HPV EN BELGIQUE MÈNE À UNE HAUSSE IMPORTANTE DES TESTS DE SUIVI. 14 -- 10. UN DÉPISTAGE PAR HPV TOUS LES 5 ANS SERAIT PLUS COÛT-EFFICACE QU’UN DÉPISTAGE PAR PAP-TEST TOUS LES 3 ANS TEL QUE RECOMMANDÉ ACTUELLEMENT. 14 -- RECOMMANDATIONS 16

282 p., ill, LIST OF FIGURES 7 -- LIST OF TABLES 13 -- LIST OF ABBREVIATIONS .20 --  SCIENTIFIC REPORT .22 -- 1 OPTIMAL FIRST SCREENING TEST .22 -- 1.1 UPDATE ON ACCURACY OF HPV VS. CYTOLOGY SCREENING 22 -- 1.1.1 Introduction .22 -- 1.1.2 Methods.24 -- 1.1.3 Results 25 -- 1.1.4 Relative cross-sectional accuracy 36 -- 1.1.5 Cross-sectional outcomes of randomised trials comparing cytology with HPV based screening 39 -- 1.1.6 Discussion 41 -- 1.2 EFFICACY AND EFFECTIVENESS OF HPV VS CYTOLOGY IN PRIMARY SCREENING FOR CERVICAL CANCER 42 -- 1.2.1 Introduction .42 -- 1.2.2 Clinical questions .42 -- 1.2.3 Results 43 -- 2 SCREENING INTERVAL FOR CYTOLOGICAL OR VIROLOGICAL SCREENING FOR CERVICAL CANCER .49 -- 2.1 SCREENING INTERVALS PROPOSED IN CURRENT GUIDELINES FOR CYTOLOGICAL SCREENING .49 -- 2.2 LOW RISK OF CERVICAL PRE-CANCER AND CANCER AFTER A NEGATIVE HRHPV DNA TEST OBSERVED IN SCREENED COHORTS .49 -- 2.3 INCREASED PROTECTION AGAINST CERVICAL CANCER DEMONSTRATED IN RANDOMISED TRIALS .52 -- 2.4 CONCLUSION 52 -- 3 TARGET AGE GROUP FOR CYTOLOGICAL OR VIROLOGICAL SCREENING FOR CERVICAL CANCER .53 -- 3.1 TARGET AGE GROUP PROPOSED IN CURRENT GUIDELINES FOR CYTOLOGICAL SCREENING .53 -- 3.2 AGE-SPECIFIC PREVALENCE OF HPV INFECTION 55 -- 3.3 VARIATION IN TEST ACCURACY OF CERVICAL CYTOLOGY AND HRHPV DNA TESTING BY AGE 57 -- 3.4 INFLUENCE OF AGE ON SCREENING EFFICACY 61 -- 3.5 AGE-SPECIFIC ADVERSE EFFECTS RELATED TO TREATMENT OF SCREEN-DETECTED LESIONS .61 -- 3.6 AGE TO STOP SCREENING 62 -- 3.7 CONCLUSION 63 -- 4 TRIAGE OF WOMEN WITH A POSITIVE HPV TEST AT SCREENING 63 -- 4.1 INTRODUCTION .63 -- 4.2 MATERIALS AND METHODS .63 -- 4.2.1 Clinical question 63 -- 4.2.2 Literature Search 64 -- 4.2.3 Statistical analysis 64 -- 4.3 RESULTS 65 -- 4.3.1 Literature retrieval 65 -- 4.3.2 Absolute accuracy of cytology and/or hrHPV-DNA based triage algorithms .67 -- 4.3.3 Triage with a combination of reflex cytology (cut-off ASC-US+) and HPV16 or HPV1618 genotyping 70 -- 4.3.4 Triage with reflex cyto

27 p., ill, FOREWORD 1 -- ABSTRACT 2 -- SYNTHESIS 4 -- 1. INTRODUCTION 6 -- 1.1. BACKGROUND 6 -- 1.1.1. Incidence 6 -- 1.1.2. Mass screening 6 -- 1.1.3. Caused by HPV 6 -- 1.1.4. Pap test 6 -- 1.1.5. HPV test 7 -- 1.2. THE PROBLEM ADDRESSED BY THIS REPORT. 7 -- 2. FINDINGS 8 -- 2.1. WHAT IS THE OPTIMAL SCREENING ALGORITHM FOR CERVICAL CANCER SCREENING 8 -- 2.1.1. Update on accuracy of HPV vs. cytology screening 8 -- 2.1.2. Efficacy of HPV-based compared to cytology-based screening 8 -- 2.1.3. Clinically validated HPV assays 9 -- 2.1.4. Screening interval: low risk of cervical pre-cancer and cancer after a negative hrHPV DNA test observed in screened cohorts 9 -- 2.1.5. Age to start HPV screening 10 -- 2.1.6. Triage algorithms 11 -- 2.2. ORGANISATION OF THE CERVICAL SCREENING IN BELGIUM 12 -- 2.2.1. Organisation in general 12 -- 2.2.2. Quality control of cytology 12 -- 2.2.3. Quality control of HPV 13 -- 2.3. CERVICAL SCREENING IN BELGIUM 13 -- 2.3.1. Introduction 13 -- 2.3.2. Consumption based on IMA data 14 -- 2.3.3. General cytological and HPV results 15 -- 2.3.4. Cyto-virological relation 18 -- 2.3.5. Cytohistological relation 20 -- 2.4. COST IMPLICATIONS 21 -- 2.4.1. Introduction 21 -- 2.4.2. Results 22 -- 2.4.3. Discussion and conclusion 23 -- 3. KEY POINTS AND RECOMMENDATIONS 23 -- 3.1. KEY POINTS 23 -- RECOMMENDATIONS 24 -- REFERENCES 25

17 p., ill, Er bestaat een duidelijk verband tussen baarmoederhalskanker en de aanwezigheid van een lokale infectie met het humaan papillomavirus (HPV), dat seksueel wordt overgedragen. Het KCE (Federaal Kenniscentrum voor de Gezondheidszorg) stelde, samen met het Wetenschappelijk Instituut Volksgezondheid (WIV) en het Kankerregister, vast dat een screening met de HPV-test, die het virus opspoort, vrouwen ouder dan 30 jaar beter beschermt tegen baarmoederhalskanker dan de klassieke uitstrijkjes (ook Pap-test genoemd), en dit aan een lagere kost. Bovendien zou de HPV-test de duur tussen 2 onderzoeken in alle veiligheid kunnen verlengen van 3 tot 5 jaar. Belangrijk is daarbij dat alle vrouwen tussen 25 en 64 jaar zich verder laten screenen. Dat geldt ook voor vrouwen die werden gevaccineerd tegen het HPV-virus, omdat het vaccin niet beschermt tegen alle virustypes en de werkingsduur van het vaccin nog onvoldoende is gekend., VOORWOORD 2 -- ONDERZOEKSVRAGEN 3 -- KERNBOODSCHAPPEN 3 -- CONTEXT 4 -- RESULTATEN 6 -- 1. DE HPV-TEST IS GEVOELIGER DAN DE PAP-TEST VOOR DE OPSPORING VAN PRECANCEREUZE CIN2- EN CIN3-LETSELS. ZIJN SPECIFICITEIT IS DAARENTEGEN LAGER. 6 -- 2. HET BESCHERMENDE EFFECT VAN DE HPV-TEST TEGEN INVASIEVE KANKERS IS DUIDELIJK HOGER DAN DAT VAN DE PAP-TEST, OP BASIS VAN GERANDOMISEERDE KLINISCHE STUDIES. DIT VOORDEEL IS NIET AANGETOOND BIJ VROUWEN JONGER DAN 30 JAAR 7 -- 3. HET SCREENINGSINTERVAL KAN MET DE HPV-TEST IN ALLE VEILIGHEID WORDEN VERHOOGD TOT 5 JAAR EN MEER. 8 -- 4. HET AANBEVOLEN ALGORITME VOOR EEN GEORGANISEERDE SCREENING: EEN TRIAGESTRATEGIE IN TWEE STAPPEN, MET EEN HPV-TEST ALS EERSTE TEST EN TWEE PAP-TESTEN BIJ EEN ASC-US RESULTAAT OF EEN HOGERE GRAAD 8 -- 5. CYTOLOGISCHE TESTEN: ER BESTAAT GEEN KWALITEITSCONTROLE VAN HUN INTERPRETATIE. 9 -- 6. HPV-TESTEN: ISO-15189-ACCREDITATIE NODIG VOOR TERUGBETALING, MAAR HET SYSTEEM STAAT NOG NIET HELEMAAL OP PUNT. 10 -- 7. DE HUIDIGE SCREENING IS NIET EFFICIËNT: ER WORDEN TE WEINIG VROUWEN GESCREEND, EN DEZEN WORDEN DAN WEER TE VAAK GESCREEND. ER WORDEN TE VEEL COLPOSCOPIEËN UITGEVOERD 10 -- 8. GROOT VERSCHIL IN PERCENTAGE AFWIJKENDE CYTOLOGIERESULTATEN TUSSEN DE LABORATORIA. 12 -- 9. KANS KLEIN DAT HET INVOEREN VAN HPV-TESTEN IN BELGIË LEIDT TOT EEN BELANGRIJKE VERHOGING VAN HET AANTAL FOLLOW-UP TESTEN.14 -- 10. EEN VIJFJAARLIJKSE SCREENING MET DE HPV-TEST ZAL KOSTENEFFECTIEVER ZIJN DAN EEN DRIEJAARLIJKSE SCREENING MET DE PAP-TEST, WAT VANDAAG WORDT AANBEVOLEN 14 -- AANBEVELINGEN 16

130-134, The increased thyroid cancer incidence observed worldwide is, at least to some extent, attributed to increased detection, with considerable regional variations. We investigated whether regional variations in cancer incidence in Belgium were associated with variations in thyroid disease management, using a retrospective population-based cohort study. A regional variation in the use of thyroid imaging and surgery was revealed, supporting differing detection rates as a key determinant of the geographic variations in thyroid cancer incidence.

info:eu-repo/semantics/published

info:eu-repo/semantics/published

A101-A102, Worldwide, the increase in thyroid cancer incidence is paralleled by the increasing power of detection owing thyroid-imaging modalities and FNAC. Besides this temporal variation, large geographical variations exist and might be similarly associated with increased detection. Here we studied variations in use of screening exams leading to detect functional or structural thyroid abnormalities in Belgium, a western European country (11,000,000 inhabitants) with mild iodine deficiency. The Belgian Cancer Registry (BCR) reported marked geographical variations in thyroid cancer incidence, with a European Standardized Incidence Rate (ESR) of 3.3 and 6.7 per 100,000 person years (py) in the North (Flanders) and the South (Wallonia), respectively, further designated as low- and high- incidence regions (LIR and HIR). This geographical difference was mainly explained by an increased proportion of small (T1) papillary thyroid cancers [ESR of T1 PTC of 1.4 and 4.1 per 100,000 py in the LIR and HIR, respectively (BCR 2004-2006)]. A representative sample of the Belgian health insurance database (2003-2008) was used to calculate the age-standardized rate of tests potentially leading to the discovery of thyroid disease (serum TSH, neck ultrasound, carotid duplex, CT, or MRI, or PET), both in the global population residing in the LIR and HIR, and in a restricted population (excluding individuals with a history of thyroid disease). In the global population, the TSH testing rate was lower in the LIR compared to the HIR. However, the difference was not statistically (Table Presented) significant in the restricted population [338.3 (95%CI 337.2-339.4) vs. 350.1 (95%CI 348.6-351.7) per 1,000 py, p = 0.3]. The rate of imaging procedures potentially unmasking an occult thyroid tumor was significantly lower in the LIR compared to the HIR, both in the global population as well as in the restricted population (p < 0.0001) (see Table for the restricted population). Geographical thyroid cancer in

136 p., Ill.

136 p., Ill.

26 p., Ill., In Wallonië en Brussel worden er dubbel zoveel gevallen van schildklierkanker vastgesteld dan in Vlaanderen. De minister van Volksgezondheid vroeg het Wetenschappelijk Instituut Volksgezondheid (WIV) en het Federaal Kenniscentrum voor de Gezondheidszorg (KCE) om dit verschil te onderzoeken, samen met de Stichting kankerregister. In april 2012 concludeerde het WIV dat wonen in de buurt van een kerncentrale geen verhoogd risico vormt. Het KCE, van zijn kant, stelt vast dat er in Brussel en vooral in Wallonië meer beeldvormingstechnieken en operaties bij de diagnose en behandeling van schildklieraandoeningen worden uitgevoerd. Dit verhoogt sterk de kans dat schildklierkanker in een vroeg stadium toevallig wordt ontdekt. Het zou een verklaring kunnen zijn voor het regionale verschil, maar dit vraagt nog meer diepgaand onderzoek. Het KCE pleit voor het algemeen toepassen van de internationale klinische praktijkrichtlijnen. Dit zou de regionale verschillen sterk doen verminderen, en ervoor zorgen dat waardevolle pre-operatieve technieken meer worden gebruikt.

26 p., Ill., L’incidence des cancers de la thyroïde est deux fois plus élevée en Wallonie et à Bruxelles qu’en Flandre. La Ministre de la Santé Publique a demandé à l’Institut Scientifique de Santé Publique (ISP) et au Centre fédéral d’expertise des soins de santé (KCE) d’analyser cette variabilité géographique, en collaboration avec la Fondation Registre du Cancer (BCR). En avril 2012, l’ISP a conclu que vivre aux alentours d’installations nucléaires n’augmentait pas le risque de développer un cancer de la thyroïde. Le KCE a, pour sa part, observé qu’à Bruxelles et plus particulièrement en Wallonie, plus d’examens d’imagerie médicale et d’interventions chirurgicales sont réalisés pour le diagnostic et le traitement des pathologies de la thyroïde. Ce recours intensif augmente les chances de découvrir de manière fortuite un cancer de la thyroïde à un stade de développement précoce. Cela pourrait justifier les différences d’incidence observées entre régions mais une étude approfondie reste nécessaire pour confirmer cette conclusion. Le KCE plaide pour l’amélioration du suivi des recommandations internationales dans la prise en charge des pathologies thyroïdiennes. Cela contribuerait à réduire fortement les différences régionales et conduirait à une utilisation plus fréquente des procédures pré-opératoires recommandées.

pp. 9, Context: Increased thyroid cancer incidence is at least partially attributed to increased detection and shows considerable regional variation. Objective: We investigated whether regional variation in cancer incidence was associated with variations in thyroid disease management. Design: We conducted a retrospective population-based cohort study that involved linking data from the Belgian Health Insurance database and the Belgian Cancer Registry to compare thyroidrelated procedures between regions with high and low cancer incidence. Main Outcome Measures: Primary outcome measures were rates of TSH testing, imaging, fineneedle aspiration cytology (FNAC), and thyroid surgery. Secondary study outcomes were proportions of subjects with thyrotoxicosis and nodular disease treated with surgery, of subjects treated with surgery preceded by FNAC or with synchronous lymph node dissection, and of thyroid cancer diagnosis after surgery. Results: The rate of TSH testing was similar, but the rate of imaging was lower in the low incidence region. The rate of FNAC was similar, whereas the rate of surgery was lower in the low incidence region (34 [33; 35 ] vs 80 [79; 81 ] per 100 000 person years in the high incidence region; P _ .05). In the low incidence region compared to the high incidence region, surgery represented a less chosen therapy for euthyroid patients (47 [46–48] vs 69 [68–70]; P _ .05), proportionally more surgery was preceded by FNAC, more cancer was diagnosed after total thyroidectomy, and thyroid cancer patients had more preoperative FNAC and synchronous lymph node dissection. Conclusion: Regional variation in thyroid cancer incidence, most marked for low-risk disease, is associated with different usage of thyroid imaging and surgery, supporting variable detection as a key determinant in geographic variation.

The main objective of this project was to estimate progression-free survival rates at different fixed time points in order to design future phase-II trials targeting the progression-free survival rate as primary endpoint in mesothelioma. Response rate has traditionally been used as an endpoint in many phase-II trials of oncology therapies. However, progression-free survival could be a more appropriate endpoint in rapidly progressing disease, at least in three situations: (1) when testing cytostatic agents, (2) when the response to a regimen is difficult to assess, (3) when the response is expected to be low. The use of progression-free survival as an endpoint instead of the response rate is relevant in mesothelioma for two primary reasons. Firstly, the global incidence of mesothelioma is increasing and current treatments yield disappointingly poor results. The development of more active treatments is thus highly desirable and new targeted therapies, including cytostatic agents, are currently the main focus of mesothelioma research. Secondly, in mesothelioma the assessment of response is difficult and not reproducible, and the response rate is usually low. In order to evaluate a novel therapy using progression-free survival rate as the primary endpoint, we need data about the progression of patients and especially about the progression-free survival rate at fixed time point. Data on 523 patients included in 10 mesothelioma trials conducted by the European Organisation for Research and Treatment of Cancer were analysed. Values of progression-free survival rate at 3, 4, 5 and 6 months in groups of different levels of therapeutic activity and in different risk groups were calculated. Our work also provides a prognostic index which allows the definition of more homogeneous groups of patients that avoids dilution of results between groups. Based on these results, the size of future mesothelioma trials can be calculated and designs can be adapted to improve the assessment, (MED 3) -- UCL, 2010

PURPOSE: For cytostatic agents or when the response assessment is difficult, adaptations to phase II designs may allow a better assessment of therapeutic activity: first by using the progression-free survival rate (PFSR) as primary end-point instead of the response rate, and second by considering progression-free survival (PFS) risk groups based on a prognostic index (PI). In mesothelioma, current treatments yield disappointingly poor results and there is a need to investigate new regimens. The purpose of this report is to provide a PI for PFS in mesothelioma and reference values for the PFSR. MATERIALS AND METHODS: Data on 523 patients included in 10 European Organisation for Research and Treatment of Cancer (EORTC) mesothelioma studies were analysed to identify prognostic factors using a multivariate Cox regression model. Subsequently, a PI and a nomogram for PFS were developed. The PFSRs at 3, 4, 5 and 6 months were estimated. RESULTS: A performance status>0, stage IV disease and mixed or sarcomatous histological type were indicators of a poor prognosis for PFS. From the PI, based on these three variables, four risk groups were defined. The median progression-free survival ranged from 5.3 to 2.1 months in these risk categories. The PFSRs at 3 months were 70.6%, 62.4%, 54.2% and 42.1% in the four categories, respectively. CONCLUSION: The PI allows dividing patients into homogeneous risk categories in which PFSRs can be calculated and used to design future phase II mesothelioma trials. Defining homogeneous categories of patients avoids dilution of results between groups and improves the assessment of therapeutic activity.

Purpose: For cytostatic agents or when the response assessment is difficult, adaptations to phase II designs may allow a better assessment of therapeutic activity: first by using the progression-free survival rate (PFSR) as primary end-point instead of the response rate, and second by considering progression-free survival (PFS) risk groups based on a prognostic index (PI). In mesothelioma, current treatments yield disappointingly poor results and there is a need to investigate new regimens. The purpose of this report is to provide a PI for PFS in mesothelioma and reference values for the PFSR. Materials and methods: Data on 523 patients included in 10 European Organisation for Research and Treatment of Cancer (EORTC) mesothelioma studies were analysed to identify prognostic factors using a multivariate Cox regression model. Subsequently, a PI and a nomogram for PFS were developed. The PFSRs at 3, 4, 5 and 6 months were estimated. Results: A performance status > 0, stage IV disease and mixed or sarcomatous histological type were indicators of a poor prognosis for PFS. From the PI, based on these three variables, four risk groups were defined. The median progression-free survival ranged from 5.3 to 2.1 months in these risk categories. The PFSRs at 3 months were 70.6%, 62.4%, 54.2% and 42.1% in the four categories, respectively. Conclusion: The PI allows dividing patients into homogeneous risk categories in which PFSRs can be calculated and used to design future phase II mesothelioma trials. Defining homogeneous categories of patients avoids dilution of results between groups and improves the assessment of therapeutic activity. © 2009 Elsevier Ltd. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

Chromosomal translocations represent an important prognostic indicator in B-cell chronic lymphocytic leukemia (B-CLL). However, their value had been neither determined in homogeneously treated patients nor compared to that of IgVH mutational status. Sixty-five B-CLL patients were investigated using cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of IgVH and of TP53 mutational status before treatment with 2-chloro-2′-deoxyadenosine (CdA). Translocations (n=45) were detected in 42% of the patients, including both balanced (n=12) and unbalanced (n=33) types. IgVH was mutated in 43% of the patients. Patients with translocations were more heavily pretreated (P=0.05), presented with more complex karyotypes (P=0.001), 17p abnormalities and TP53 mutations, and had a higher failure rate (59 vs 21% in patients without translocations, P<0.004). Patients with unbalanced translocations displayed a shorter median treatment-free survival (TFS, 6.9 vs 35.9 months, log rank 22.72, P<0.001) and overall survival (OS, 13.0 vs 68.0 months, log rank 16.51, P<0.001), as compared to patients without translocation. In multivariate analysis, unbalanced translocations were independently associated with therapeutic failure, short TFS and short OS. IgVH mutational status was independently associated with risk of failure and TFS, but not OS. In B-CLL patients treated with CdA, translocations are strong predictors of outcome., SCOPUS: ar.j, info:eu-repo/semantics/published