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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
Grazie per l’attenzione