Hodgkin Flashcards
Avoid RT in PET negative early stage? RAPID
UK NCRI RAPID:
“Observation is not noninferior to IFRT in early stage HL with negative PET after chemo, and PFS favored IFRT.
Stage IA-IIA “ABVD x3 → PET →
→PET positive: ABVD x1 +IFRT
→PET negative: IFRT vs. obs
Primary endpoint: noninferiority of PFS, delta of 7% in CI”
"CR in 75% PET negative (IFRT vs. obs): 3-yr PFS favors RT, 95% vs. 91% (CI exceeded noninferiority boundary of 7) 3-yr OS 97% vs. 99% (p=-.21)
Per protocol analysis
(12% in RT arm ““declined”” RT)
3-yr PFS 97% vs. 90%
PET score of 5 was the best predictor of prognosis. PET score of 1-4, EORTC or GHSH favorable vs. unfavorable not predicitive”
Avoid RT in PET negative early stage? GELA H10
EORTC LYSA GELA H10 F/U: Observation is not noninferior to INRT in early stage HL with negative PET after chemo, and PFS favored INRT.
Stage I-II HL “ABVD x2 → PET →
→Standard, non-PET directed:
ABVD (x1 for F, x2 for U) + 30-36 Gy INRT
vs.
→PET directed INRT:
PET positive: BEACOPP x2 + 30-36 Gy INRT
PET negative: additional ABVD (total x6 for U, total x4 for F)
Primary endpoint: noninferiority of PFS, delta of 10%”
“-86% achieved CR. In unfavorable 75% had CR
-PFS improved in standard arm vs PET negative arms. PET negative arm stopped early at 1-yr analysis
PET negatives (standard vs. directed):
- favorable 5-yr PFS 99% ABVD+INRT vs. 87% ABVD
- unfavorable 5-yr PFS 92% vs. 90%
- With ABVD alone, 73% failures were soley at original sites
PET positives (standard vs. directed): 5-yr PFS 77% with standard ABVD+INRT vs. 91% BEACOPPesc+INRT"
Avoid RT in PET negative early stage? HD16
HD16 GHSG: “Observation is not noninferior to IFRT in favorable HL with negative PET2 after chemo. PFS favors RT. Positive PET is a risk factor for recurrence.”
Stage I-II HL, favorable “ABVD x2 → PET →
→Standard, non-PET directed: 20 Gy IFRT vs. →PET directed IFRT: if PET positive: 20 Gy IFRT PET negative: no RT
Primary endpoint: noninferiority of PFS”
PET negatives (standard vs. directed): 5-yr PFS 93% IFRT vs. 86% no RT -Infield recurrence 2% vs. 9% -No difference in outfield recurrence, 5-4% both arms 5-yr OS 98% both arms
- If using Deauville 4 as cutoff:
- In ABVD+IFRT, 5-yr PFS in PET negative was 93% and 5-yr PFS in PET positive was 80%”
Can INRT be omitted in negative PET after escBEACOPP + ABVD?
HD17 GHSG: “INRT can be safely omitted in negative PET after treatment with escBEACOPP + ABVD. PET-guided INRT is noninferior to routine IFRT in PFS and OS.”
“Stage I-II HL, unfavorable
“escBEACOPP x2 + ABVD x2 → PET →
→Standard, non-PET directed: 30 Gy IFRT vs. →PET directed INRT: PET positive: 30 Gy INRT PET negative: no RT
“Results noninferior
5-yr PFS 97% vs. 95%
5-yr OS 98% both arms
Details on RT to be published separately”
STLI vs. chemo in early stage?
HD6 GHSG: Treatment with chemo alone had superior OS compared to RT with STLI in early stage HL. With STLI 20 died of other causes (6 had chemo), leading to inferior OS.
Stage IA or IIA, non-bulky”
→ABVD x4-6
vs.
→35 Gy STLI (For unfavorable risk, another +2 ABVD before STLI)”
“Improved OS and EFS with chemotherapy, and improved FFP with RT:
12-yr OS 94% vs. 87%, p=0.04
12-yr FFP 87% vs. 92%, p=0.05
12-yr EFS 85% vs. 80%
Death due to second cancers: 4 vs. 10
Other causes (not 2nd cancer): 2 vs. 10
Cardiac events: 16 vs. 26
On subanalysis, the difference is in unfavorable risk but not in favorable “
Determined Dose of RT and Cycles of ABVD for early stage Hodgkin?
HD10 GHSG: Regimens are noninferior. 20 Gy RT with 2 cycles ABVD, the most de-escalated option, should be preferred in favorable HL.
Early-stage favorable HL (7.5% of patients had ESR<30 with B symptoms)" →ABVD x2 vs. →ABVD x4 →IFRT 20 Gy vs. →30 Gy Noninferiority [prior to PET era]"
"No significant differences in outcomes 5-yr FFTF ~92% 10-yr OS 94% 10-yr PFS 87% No differences in secondary malignancy at 10 years"
Determined BEACOPP vs ABVD, Radiation Dose?
HD11 GHSG: “ABVD + 30 Gy and BEACOPP + 20 Gy are preferred treatment options for unfavorable HL. Among the arms found noninferior, these have the least toxicity. Increased toxicity with BEACOPP compared to ABVD. Increased toxicity with 30 Gy compared to 20 Gy IFRT.”
Unfavorable HL, Stage I or IIA, with ≥1 risk factor: large MS mass, extranodal disease, increase ESR, ≥3 nodal regions. Or Stage IIB with increased ESR or ≥3 nodes
“→escBEACOPP x4 vs. →ABVD x4
→IFRT 30 Gy vs. →20 Gy
Noninferiority
[prior to PET era]”
“ABVD 30 Gy, BEACOPP 20 Gy, and BEACOPP 30 Gy are noninferior.
5-yr FFTF ~86%, 5-yr OS ~95%, 5-yr PFS ~88%
ABVD 20 Gy is not noninferior.
10-yr PFS 76% ABVD 20 Gy vs. 84% in other arms
BEACOPP gave increased toxicity over ABVD:
grade ≥3, 74% vs. 52%
30 Gy gave increased toxicity over 20 Gy:
grade ≥3, 12% vs. 6%
No differences in secondary malignancy at 10 years”
BEACOPP/ABVD vs. ABVD?
HD14 GHSG: BEACOPP/ABVD + IFRT improves FFTF over ABVD + IFRT in unfavorable HL.
Stage IA-IIB with at least one risk factor
“→escBEACOPPx2 + ABVDx2 + IFRT 30 Gy
vs.
→ABVD x4 + IFRT 30 Gy”
“FFTF and PFS improved with BEACOPP/ABVD:
5-yr FFTF 95% escBEACOPP/ABVD vs. 88% ABVD
on subanalysis, benefit only in bulky or B sx
5-yr PFS improved by 6%
5-yr OS 97% in both arms
relapses 3% vs. 8%
acute toxicity increased, late toxicity not different”
RT dose, omission of RT in early stage?
EORTC GELA H9F: After CRu in favorable HL, RT results in superior RFS compared to observation.
favorable I-IIB HL
“After 6 cycles EBVP and CRu:
36 Gy IFRT vs. 20 Gy vs. no RT
No RT arm stopped early due to high recurrences >20%”
“Worse RFS with obs. 20 Gy and 36 Gy noninferior
5-yr RFS 89% vs. 84% vs. 70%
5-yr OS same at 97-100%”
BEACOPP vs. ABVD?
EORTC GELA H9U: Outcomes are noninferior. BEACOPP has more toxicity. ABVD x4 + IFRT is the preferred regimen.
Unfavorable stage I-II HL (age ≥50, 4-5 sites, bulky, ESR ≥50 no B-symptoms, ESR ≥30 and B-symptoms)
“ABVD x6 + IFRT vs. ABVD x4 + IFRT vs. BEACOPPbaseline x4 + IFRT
RT to 30 Gy ±boost”
“5-yr EFS noninferior: 85.9% vs. 88.8% vs. 89.9%
5-yr OS 93-94% (NS)
BEACOPP regimens result in worse toxicity”
Dose reduction RT early stage?
HD4 GHSG: De-escalation to 30 Gy from 40 Gy shows favorable outcomes.
Hodgkin lymphoma Stage I-II
“40 Gy EFRT + 40 Gy IFRT
vs. 30 Gy EFRT + 40 Gy IFRT”
“No difference in RFS or OS.
RFS 78% vs. 83% (p=0.093),
OS 91% vs. 96% (p=0.16)”
STNI vs. IFRT
EORTC H7F & H7U
EORTC H8F & H8U
HD8 GHSG: IFRT has similar PFS and OS to EFRT. IFRT is preferred.
RT, BEACOPP regimen in Advanced?
HD12 GHSG: RT improves FFTF in advanced HL with PR compared to no further treatment. BEACOPPesc seems preferred to BEACOPPbase.
Advanced stage
“→BEACOPPesc x8
vs.
→BEACOPPesc x4 + BEACOPPbase x4→ if bulky or PR, RT vs. no RT”
“5-yr FFTF ~85% in BEACOPP arms, not different (however at early f/u BEACOPPbase was slightly worse)
5-yr FFTF 90% with RT vs. 87%, p=0.08
On subanalysis RT did benefit those with PR on CT, and not bulky disease.”
BEACOPP regemin, Benefit of RT in advanced?
HD15 GHSG: BEACOPPesc x6 followed by PET guided RT led to improved FFTF and is preferred. PET can guide the use of RT.
newly diagnosed advanced stage HL
“BEACOPPesc x8
vs. BEACOPPesc x6
vs. BEACOPP(14) x8
If persistant mass size ≥2.5 cm and active on PET, 30 Gy RT given as per HD12”
“5-yr FFTF 84% vs 89% vs 85%
(noninferior in 6xBesc and 8xB(14) compared to 8xBesc)
5-yr OS 92% vs 95% vs 95%
(improved with 6xBesc over 8xBesc)
8xBesc had higher deaths due to toxicty
12-mo NPV with PET 94%. 11% received additional RT”
RT after CR in Advanced?
EORTC 20884/GPMC H34: IFRT did not improve EFS in advanced HL with CR. RT in PR led to OS matching those with CR.
Stage III-IV HL with CR or PR after MOPP-ABV
“CR (60%): obs vs. 16-24 Gy IFRT
PR: single arm 18-30 Gy”
“No change in 5-yr EFS (77% vs. 73%) or OS (85% vs. 78%) for pts with CR. Similar outcomes for those with PR (76% and 84%).
5-yr rate of second cancers 5% vs. 8% with RT, p=0.05”
