Non-Hodgkin Flashcards
CHOP vs CHOP+RT?
ECOG 1484: Adding RT to chemo improves LC and DM compared to chemo alone in NHL, with trend to benefit in FFS and TTP. Giving RT to all PR results in favorable outcomes.
Risky Stage I, or IE-IIE aggressive lymphoma
“→CHOP x8 + 30 Gy IFRT
vs.
→CHOP x8
40 Gy IFRT for all PRs in both arms (28%)”
"In CR pts, DFS improved with IFRT 6-yr DFS 73% IFRT vs. 56%, p=0.05 Any LR 17% vs. 48% FFS and TTP favored RT, p=0.06 in both Distant relapse 82% vs. 52% 6-yr FFS 63% in PRs "
CHOPx3+RT vs CHOPx8?
SWOG 8736: Adding RT to chemo improves PFS and OS compared to chemo alone in NHL at 5 years. However the benefit is lost on long-term f/u.
Intermediate-grade stage I-IIE NHL, including bulky (≥10 cm) stage I
“→CHOP x3 + 40-55 Gy IFRT (most had 40-50 Gy)
vs.
→CHOP x8”
"5-yr PFS 77% IFRT vs. 64% 5-yr OS 82% vs. 72% No infield relapses No difference 10-yr PFS or OS At long term f/u PFS never plateaus Excess late failures occurred out of field in the CHOPx3+IFRT arm"
CHOPx4 vs CHOPx4+RT?
GELA LNH 93-4L Adding RT to chemo did not improve EFS or OS in elderly patients with NHL.
age >60 with Stage I-II aggressive lymphoma and IPI=0
“→CHOP x4 + 40 Gy IFRT
vs.
→CHOP x4”
“No benefit in EFS or OS with RT. RT improved LC but DM was worsened
5-yr EFS 64% vs. 61% (NS)
5-yr OS 72% vs. 68% (NS)
Isolated LR 21% vs. 47%
Any LR: 34% vs. 63%
Distant recurrence: 79% vs. 53%”
RCHOP vs RCHOP+RT?
LYSA/ GOELAMS 02-03: R-CHOP alone is noninferior to R-CHOP plus RT in nonbulky limited stage DLBCL.
“Limited stage non bulky (<7 cm) DLBCL
(~95% were IPI 0-1)”
“→R-CHOP-14 x4 or 6 cycles + 40 Gy IFRT
vs.
→R-CHOP-14 x4 or 6 cycles
PET used to assess CR/PR
40 Gy IFRT for all PRs in both arms. 4 cycles chemo for 0 prognostic factors and 6 cycles for ≥1 factors.”
"Arms are noninferior 5-yr EFS 89% vs. 92% RT (p=0.18) 5-yr OS 92% vs. 96% RT (p=0.28) 13 relapses in no RT arm, 5 at initial site 10 relapses in RT arm, none in field"
RCHOP vs RCHOP +RT NCBD
Chemo alone was associated with worse OS compared to when RT was given with chemo. Randomized trials are required for confirmation as adjustments for imbalances in database studies cannot remove all confounding variables.
Stage I-II DLBCL. 46% Stage II, 42% extranodal, 58% >60
“→NCDB analysis of patients treated from 1998-2012
chemo + RT
vs.
→chemo alone “
“OS improved with use of RT
Estimated 5-yr OS 82% chemoRT vs. 75% chemo
10-yr OS 64% vs. 55%
OS benefit for RT remained after adjustment for immortal times and indication bias (HR 0.66)
Use of RT declined from 47% in 2000 to 32% in 2012”
Elderly 6vs8 cycles, CHOP vs RCHOP, RT to bulky?
RICOVER-60 DSHNHL: “In early NHL in ages 61-80, R-CHOP is superior to CHOP. There is no benefit to more than 6 cycles. PET was not required in this study.
RT to bulky sites improves EFS. On per protocol analysis, there is benefit in OS and PFS.”
“Any stage and any IPI aggressive B cell NHL, age 61-80 (Stage I-II=50%, Stage III-IV=50%)”
“→CHOP-q14d x6 vs.
→CHOP-q14d x8 vs.
→R-CHOP-q14d x6 vs.
→R-CHOP-q14d x8.
Comparison of 36 Gy IFRT to bulky >7.5 cm and no RT cohorts
IFRT was initially required for bulky disease. An amendment allowed RT to be omitted once the superior arm was identified.”
“In MVA of ITT and adjusting IPI and age >70 with bulky disease, EFS omitting RT is inferior (p=0.005), and there is trend to inferior PFS (p=0.058) and OS (p=0.127).
On per protocol analysis, there is benefit to RT in EFS, PFS, and OS, HR 4.3, p=0.002.
No benefit to 8 cycles
Addition of R to CHOP-14 x6 improved EFS, PFS, and OS. 3-yr EFS 66%, OS 88%”
Can RT be omitted in PET negative bulky disease elderly?
OPTIMAL>60 DSHNHL: RT can be omitted in PET negative patients with bulky disease.
Any stage and any IPI aggressive B cell NHL, age 61-80
“→RCHOP-q14d vs.
→Opti-RCHOP-q14d vs.
→RCHOP liposomal vincristine vs.
→Opti-RCHOP liposomal vincristine
PET positive >7.5 cm bulky received 39.6 Gy RT. No RT for PET negative bulky. Compared to RICOVER results”
“48% were PET positive after chemo
Interim analysis
PFS: PET positive no RT 35% vs. PET positive with RT 70% vs. PET negative no RT 80%
When compared to RICOVER-60 patients, results were noninferior. Characteristics were balanced.”
RT for bulky disease in younger, IPI 0-1?
UNFOLDER 21/14 DSHNHL: “In early bulky or extranodal NHL in ages 18-60, RT improves EFS. There is no benefit in OS or PFS. RT could be reserved for PR. There is no difference in RCHOP q14 days or q21 days.”
IPI 0-1, aggressive B-cell NHL, age 18-60 "→RCHOP-q21d x6 vs. →RCHOP-q21d x6 +39.6 Gy if CR vs. →RCHOP-q14d x6 G-CSF vs. →RCHOP-q14d x6 G-CSF +39.6 Gy if CR
- RT to bulky or extranodal sites only
- Bulky disease (>7.5 cm) or extranodal are randomized to all arms.
- Nonbulky patients are randomized in chemo only arms, not to RT arms. “
“•RT randomization
Closed early due to excess failures without RT
3-yr EFS 68% vs. 84% RT
(mostly due to PR triggering RT in no RT arm)
3-yr PFS 89% vs. 81%, p=0.221
3-yr OS 93% both arms, not different on MVA for LDH, Stage III/IV, B, and extranodal
•PMBCL subset 3-yr EFS 78% vs. 94% (mostly due to PR triggering RT in no RT arm) CR 84% vs. 94% PR 2% vs. 10% Progression 4% vs. 2% 3-yr PFS 90% vs. 95%, p=0.0253 3-yr OS 96-97%, not different
•Chemo randomization
No difference in EFS, PFS, or OS”
RT omission in bony disease?
GHSG (MInT, RICOVER-60): RT to lymphomy with bony involvement benefits EFS and OS. PET was not required in this study.
9 GHSG trials retrospective meta-analysis
RT gave benefit in EFS and trend in OS in patients with bony disease. Benefit retained even in Stage III/IV, ECOG>1, age >60, bulky, and extranodal >1. Rituximab did not give benefit.
Chemo-de-escalation with RT?
FLYER: RCHOP x4 + R x2 may be implemented in favorable risk aggressive B cell lymphoma. The regimen is noninferior to RCHOP x6 and toxicity is reduced.
aggressive B cell lymphoma, age 18-60, stage I-II, normal LDH, ECOG 0-1, non bulky (<7.5 cm)
"Noninferiority of PFS →RCHOP x6 vs. →RCHOP x4 + Rx2 No RT in either arm. Chemo q21d"
“Results were noninferior
3-yr PFS 93% vs. 96% in RCHOP x4 + R x2
Less heme and non-heme toxicity in R-CHOP x4”
RT dose Reduction?
UK: 30 Gy is appropriate dose for aggressive NHL, and 24 Gy for indolent NHL.
Any stage receiving local therapy for definitive or curative treatment (82% DLBCL, 67% Stage I-II, 10% received R) "→Aggressive NHL 30 Gy/ 15 fx Indolent NHL 24 Gy/12 fx vs. →40-45 Gy/ 20-23 fx for all"
“No difference in overall response rate, LF, PFS, or OS. Toxicity trended to worse in the high dose arms
Aggressive NHL: 5-yr FFLP 82% vs. 84% (NS)
5-yr OS 64% vs. 68% (NS)”
Indolent lymphoma dose
FORT: 24 Gy leads to better LC than 4 Gy for follicular or marginal zone lymphoma.
Follicular or marginal lymphoma, definitive or palliative intent
“Noninferiority
→24 Gy
vs.
→4 Gy”
“Results not non-inferior
2-yr local PFS 94% vs. 80%
5-yr local PFS 90% vs. 70%”
Palliation dose for advanced follicular
The Netherlands Cancer Institute, Amsterdam: Short course RT for palliation of Stage III-IV follicular lymphoma has favorable outcomes.
Stage III-IV follicular lymphoma
“Phase II
RT to 2 Gy x 2 or 4 Gy x 1”
“ORR 92%, CR 61%, PR 31%, SD 6%
Median TTLP 25 months”
Follicular RT
NCDB: Use of RT in follicular lymphoma is associated with improved OS. Randomized trials are required for confirmation as adjustments for imbalances in database studies cannot remove all confounding variables.
Follicular chemo
TROG 99.03: Adding R-CVP to IFRT improves PFS. OS is unchanged.
Follicular lymphoma Stage I-II, low grade. PET not required
30 Gy IFRT vs. 30 Gy IFRT + R-CVP
“10-yr PFS 41% vs. 59%
10-yr OS not different, ~90%”
