I linfomi di Hodglin Criticità nel percorso diagnostico

Transcript

1 I linfomi di Hodglin Criticità nel percorso diagnostico Attilio GUARINI U.O.C. EMATOLOGIA Istituto di Ricovero e Cura a Carattere Scientifico "ISTITUTO TUMORI GIOVANNI PAOLO II BARI

2 Hodgkin Lymphoma represents the most common malignant lymphoma in young people Histologic hallmark of the disease is the presence of the characteristic Hodgkin Reed-Sternberg (HRS) cells in classical HL and so-called lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant HL Ø HL is unique among all cancers because malignant cells are greatly out numbered by reactive cells in the tumor microenvironment and make up only approximately 1% of the tumor Ø Most patients can be cured with modern treatment strategies, although approximately 20% still have low therapeutic choices, especially after high-dose chemotherapy and haematopoietic stem cell support Ø

3

4 Classical HL: Morphology Lymphocyte rich Mixed cellularity Nodular sclerosis Lymphocyte depleted

5 Classical HL: Phenotype CD15 CD30

6 Phenotypic Profile of chl CD20 PAX5 CD3 IRF4

7 Nodular Lymphocyte Predominance Hodgkin Lymphoma

8 Morphologic gray zones in HL and NHLs

9 PERCORSO DIAGNOSTICO

10 NO AGOASPIRATI FNAB Non accettare diagnosi se non su biopsie escissionali

11 LA DIAGNOSI DI HODGKIN DEVE ESSERE SEMPRE UNA DIAGNOSI PATOLOGICAMENTE DOCUMENTATA a livello di morfologia ed immunoistochimica (biologia molecolare)

12 Istotipo VALUTAZIONE CLINICA E PROGNOSTICA DECISIONE TERAPEUTICA goal TAILORED THERAPY

13 Diagnostic Workup History Complete physical examination Confirmatory workup Ø Excisional biopsy of the lymph node Staging Workup Ø Chest x ray(pa,lat) Ø CT scan thorax,abdomen and pelvis Ø FDG PET scan

14 PET Scan has become an integral component of initial staging.

15 Information provided by PET has been recently incorporated in the lymphoma guidelines for response evaluation after completion of treatment. Useful for follow up study to evaluate residual masses,

16 Ann Harbor Stage

17 Prognostic Factors Prognostic factor for Early stage Hodgkins disease

18 Prognostic factors cont Advanced stage hodgkins lymphoma International Prognostic Score

19 Andrea Gallamini, Martin Hutchings, Luigi Rigacci, Lena Specht, Francesco Merli, Mads Hansen, et al. PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL

20 Management

21 Eichenauer DA et Al, Annals of Oncology 25 (Supplement 3): 70 75, 2014

22 Anni 70 MOPP ABVD

23 Anni 80 MOPP / ABVD Stan ford V

24 Anni 90 BEACOPP

25 Anni 2000 moab

26 Biology of Brentuximab Vedotin Vaklavas C & Forero-Torres. Ther Adv Hematol 2012;3:

27 Phase II Pivotal Study of Brentuximab Vedotin Maximum Reduction in Target Lesions 94% patients achieved tumour reduction Younes A et al. J Clin Oncol. 2012;30: P

28 Modern RT

29 INRT planning Weber et al, IJROBP 2009

30 20 CT datasets of pts with early unfavorable mediastinal HL IF-PTV and IN-PTV according GHSG guidelines Plans: 3D-CRT (AP-PA) IMRT (9 equally spaced beams) Prescription dose: 30 Gy/15 fx Koeck et al, IJROBP 2011

31 Evolution of Radiotherapy within the BEACOPP GHSG Trials 5y- EFS 88% 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 5-y EFS 90% 5-y EFS 87% 5-y EFS 89%

32 outcomes in HL Cancer 2014;120:2122-9

33 HL: Cumulative Survival (Sweden)

34 . survival rates for elderly Hodgkin lymphoma (>=60 years), are disproportionately inferior compared with younger patients Intergroup Trial E year FFS values of 82% to 89% were reported with dose- and time-intensified third-generation schedules (BEACOPP), but these improvements have so far not been extended to elderly patients. Advanced age at presentation is an independent negative risk factor.

35 Hodgkin's Lymphoma in the Elderly: Different Disease in Patients Over 60! By Volker Diehl and Andreas Engert -German Hodgkin Study Group Two hypotheses were created to explain these findings: 1) age associated factors: - increased comorbidity, therapy, - reduced tolerability of conventional - more severe toxicity - treatment-related deaths, - poorer outcome after relapse 2) biologic differences such as more aggressive histology, different anatomic distribution of involved sites, and

36 Registro AIRTUM 2013 Linfoma di Hodgkin: pazienti vivi dopo 5 anni hodgkin survivors Pazienti giovani Follow up lunghi Remissioni dopo radio-chemio terapie intensive MOPP / extended field RT / BEACOPP Follow up di trapianto autologo e allogenico Immunosoppressione

37 Il rischio di morte per linfoma dopo circa 10 anni dalla terapia, raggiunge un plateau Mentre il rischio di mortalità dovuta alle complicanze tardive legate al trattamento, continua ad aumentare dopo anni e non vi è un plateau Ng AK et al. N Engl J Med 2010;363:

38 le principali cause di mortalità : Seconde neoplasie Eventi cardiovascolari le principali cause di morbidità : Disturbi respiratori Disfunzioni ormonali Infertilità Fatigue 18.5 incremento di rischio di sviluppare seconde neoplasie comparate con la popolazione generale

39 HL: Complicanze tardive - Neoplastiche v GI v Polmone v Mammella v Cute v Testa collo v Vescica v Tiroide v SNC Dutch HL cohort

40 cosa si aspettano i clinici dal Registro Tumori Integrare i dati prodotti dai registri di patologia Consentire di seguire nel tempo i pazienti con maggiore continuità Consentire stime aggiornate sulla prognosi dei pazienti Possibilità di utilizzare i dati per gli studi retrospettivi

41 Grazie per l attenzione