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
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
Classical HL: Morphology Lymphocyte rich Mixed cellularity Nodular sclerosis Lymphocyte depleted
Classical HL: Phenotype CD15 CD30
Phenotypic Profile of chl CD20 PAX5 CD3 IRF4
Nodular Lymphocyte Predominance Hodgkin Lymphoma
Morphologic gray zones in HL and NHLs
PERCORSO DIAGNOSTICO
NO AGOASPIRATI FNAB Non accettare diagnosi se non su biopsie escissionali
LA DIAGNOSI DI HODGKIN DEVE ESSERE SEMPRE UNA DIAGNOSI PATOLOGICAMENTE DOCUMENTATA a livello di morfologia ed immunoistochimica (biologia molecolare)
Istotipo VALUTAZIONE CLINICA E PROGNOSTICA DECISIONE TERAPEUTICA goal TAILORED THERAPY
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
PET Scan has become an integral component of initial staging.
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,
Ann Harbor Stage
Prognostic Factors Prognostic factor for Early stage Hodgkins disease
Prognostic factors cont Advanced stage hodgkins lymphoma International Prognostic Score
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
Management
Eichenauer DA et Al, Annals of Oncology 25 (Supplement 3): 70 75, 2014
Anni 70 MOPP ABVD
Anni 80 MOPP / ABVD Stan ford V
Anni 90 BEACOPP
Anni 2000 moab
Biology of Brentuximab Vedotin Vaklavas C & Forero-Torres. Ther Adv Hematol 2012;3:209-225
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: 2183-2189 P
Modern RT
INRT planning Weber et al, IJROBP 2009
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
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%
outcomes in HL Cancer 2014;120:2122-9
HL: Cumulative Survival (Sweden)
. survival rates for elderly Hodgkin lymphoma (>=60 years), are disproportionately inferior compared with younger patients Intergroup Trial E2498 5-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.
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
Registro AIRTUM 2013 Linfoma di Hodgkin: 42.000 pazienti 34.000 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
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 10-20 anni e non vi è un plateau Ng AK et al. N Engl J Med 2010;363:664-675.
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
HL: Complicanze tardive - Neoplastiche v GI v Polmone v Mammella v Cute v Testa collo v Vescica v Tiroide v SNC Dutch HL cohort 1965-95
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
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