children and young people:

Transcription

1 Hodgkin lymphoma in children and young people: State of the art Professor W. Hamish Wallace RHSC 2016

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3 Childhood Cancer One-, Five- and Ten-Year Actuarial Survival (%), Children (Aged 0-14), Great Britain

4 Hodgkin s lymphoma Hodgkin lymphoma accounts for about 0.6% of all cancers diagnosed in the UK 5-6 per million children per year Uncommon <5yrs old Painless cervical lymphadenopathy - 80% Asymptomatic mediastinal disease - 60% B symptoms 32%

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7 Long-term survival after Hodgkin s lymphoma Prof. Schellong (late effects report)

8 Age distribution MSN

9 Positron Emission Tomography (PET) in Hodgkin Lymphoma

10 FDG-PET scans Negative predictive value (81-100%) is consistently reported Clearly identifying patients with an excellent prognosis Question: Can RT be safely omitted after first line chemotherapy in patients with a negative PET scan? MSN

11 EURONET-PHL-C1 Aims Can involved field RT be omitted in FDG-PET scan negative patients after two courses of OEPA in all treatment groups? Can procarbazine be substituted for intermediate and advanced stage disease groups by Dacarbazine? Maintaining event free survival for all > 90% MSN

12 EURONET-PHL-C1 Inclusion: 0-18 Yrs TG1: Stage 1A/B and 11A TG2: Stage 11B,11AE,111A,1E TG3: Stage 111B, 111E, 11BE, 1VA/B MSN

13 A Patient March 2011 (age 15 years) Six month H/O of intense pruritis of her feet Three month H/O fever, night sweats, lethargy, pallor, poor appetite and weight loss Widespread LN lower cervical, mediastinum, abdomen

14 Laura:Presentation PET/CT

15 Laura EuroNet-PHL-C1 Protocol: Treatment Group 3 (TG3) Two cycles of OEPA Four cycles of COPDAC or COPP

16 EURONET-PHL-C1 Aims Can involved field RT be omitted in FDG-PET scan negative patients after two courses of OEPA in all treatment groups? Can procarbazine be substituted for intermediate and advanced stage disease groups by Dacarbazine? Maintaining event free survival for all > 90%

17 EuroNet-PHL-C-1 PET positi ve 2 x OEPA Radiotherap y TG-1 2 COPP RA PET negativ e TG-2 R 2 COPDAC 4 COPP TG-3 R 4 COPDAC Wallace WH. UK Chief Investigator No Radiotherap y CRUK support 400K

18 Early Response Assessment PET scan

19 Radiotherapy Field and estimated doses to organs at risk

20 EuroNet-PHL-C1 Interim Analysis patients in study no patients follow up too short For meaningful analysis 2111 patients > 1 year on study no patients (#3141 F-031) TG not defined 2111 patients > 1 year on study & valid EFS and TG Analysis is by TG-as treated,

21 Early response assessment (Radiotherapy Yes/NO) 2018 patients > 1 year on study & valid EFS and TG 40 patients have no valid ERA 1 progression at ERA 39 ERA not documented Valid for RT-Analysis 1978 patients > 1 year on study & valid Treatment Group & valid RT indication TG-1: 677 nort: 418 (61.7%) RT: 259 (38.3%), TG nort: 216 (48.3%) RT: 231 (51.7%) TG-3: 854 nort: 281 (32.9%) RT: 573 (67.1%)

22 Chemotherapy randomisation (TG2/3) 2018 patients > 1 year on study & valid Treatment Group 696 no further Chemotherapy TG patients Consolidation CT assigned & > 1 year on study & valid Treatment Group 941 patients randomised > 1 year on study & valid Treatment Group COPP 473 TG-2: 163 TG-3: 310*, COPDAC 468 TG-2: 163 TG-3: 305**

23 Overall Survival and Event free Survival,

24 Comparison of TGs,

25 COPP versus COPDAC randomised,

26 Radiotherapy assigned by ERA,

27 Summary Results stable None of the formal stopping rules are fulfilled EFS ~85%,

28 TL-1: Fourth interim analysis,

29 EuroNet-PHL-C2 final protocol EuroNet-PHL-C2 provides a comprehensive first line treatment strategy for all classical HL children and adolescents in Europe Standard chemotherapy consists of 2 OEPA ( for all patients ) and additional 0, 2 or 4 consolidation cycles with COPDAC-28 for early, intermediate and advanced stages. Patients in TG-1 HR (ESR>=30 mm/hr and/or bulk) will be treated in TL-2 Therefore we randomise intermediate and advanced stage patients (TL-2+3) between standard and intensive consolidation chemotherapy (COPDAC versus DECOPDAC). The new DECOPDAC regimen essentially adds Doxorubicin and Etoposide to COPDAC and may be understood as a less toxic variant of the BEACOPP regimen

30 COPDAC as standard treatment, 30

31 EuroNet-PHL-C2 final protocol Patients with complete metabolic response do not receive radiotherapy: Does intensified chemotherapy improve treatment results above the 90% EFS target? Patients with incomplete metabolic response are scheduled for a late response PET at the end of chemotherapy. They receive standard COPDAC-28 plus involved field radiotherapy or DEACOPDAC-21 with radiotherapy to late PET positive sites only (Deauville 3-5) minimising radiation volumes

32 COPDAC as standard treatment, 32

33 Thank You