2014 National Training NT 1406 2014 National Training NT 1406.
Role of RT in aggressive NHL 1406
-
Upload
yong-chan-ahn -
Category
Health & Medicine
-
view
270 -
download
0
description
Transcript of Role of RT in aggressive NHL 1406
![Page 1: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/1.jpg)
1
RT in Aggressive NHL
Yong Chan Ahn, MD, PhD Department of Radiation Oncology
Samsung Medical Center
Sungkyunkwan University School of Medicine
![Page 2: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/2.jpg)
Early stage DLBCL: Pre-Retuximab Era
• 4 randomized controlled trials:
SWOG 8736
ECOG 1484
GELA LNH 93-1
GELA LNH 93-4
![Page 3: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/3.jpg)
![Page 4: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/4.jpg)
![Page 5: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/5.jpg)
SWOG 8736: CHOP #8 vs. CHOP #3 + RT (40-55 Gy)
• CHOP #8: more cardio- and myelotoxicity
• CHOP #3 + RT: may be inadequate in some subgroup
• Overlap of FFS and OS between groups on update with 8.2 yrs’ F/U (Miller. ASH 2001)
![Page 6: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/6.jpg)
• Underpowered study: 172 Pts; 50% of registered Pts were not randomized; 20% of CR Pts did not receive assigned Tx
• No causes of death provided; CHOP #8 is quite toxic.
ECOG 1484: CHOP #8 ± RT (30-40 Gy)
![Page 7: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/7.jpg)
GELA LNH 93-1 (<60 years): ACBVP #3 vs. CHOP #3 + IFRT (40 Gy)
• CHOP + IFRT: 23 % of recurrences within RT field only; significantly worse than SWOG CHOP + IFRT
• ACVBP: 41% of recurrences at initial site only; significantly toxic & not justified (20% hospitalization)
![Page 8: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/8.jpg)
• Poor compliance in RT delivery: median 5 wks’ delay of RT; 12% no RT as assigned; 23% under-dosed RT
• CMT: 21% of recurrences in RT field only; 66% outside only
• CTx alone: 47% of recurrences at initial site only; 37% at distant site only
GELA LNH 93-4 (>60 years): CHOP #4 ± IFRT (40 Gy)
![Page 9: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/9.jpg)
Response Rate • Divergences in response assessments:
• Neither overall RR (N=1,198) nor CR (N=1,483) were different between groups
![Page 10: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/10.jpg)
Patterns of Failure
Trials
# Relapses
# Isolated relapses
at initial sites
Crude isolated
relapse rate
ECOG
CHOP #8 (N=93) 31 15 (48%) 16.1%
CHOP #8 + RT (N=79) 17 3 (17%) 3.8%
GELA 93-1
ACVBP (N=318) 42 17 (41%) 5.3%
CHOP #3 + RT (N=329) 78 18 (23%) 5.5%
GELA 93-4
CHOP #4 (N=277) 79 37 (47%) 13.4%
CHOP #4 + RT (N=299) 66 14 (21%) 4.7%
![Page 11: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/11.jpg)
Progression-free Survival • Heterogeneity in groups:
– ECOG 1484: insufficient data for ITT analysis
– GELA LNH 93-1: considerable differences in intensity and duration of CTx in both arms
• PFS was longer for CMT
![Page 12: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/12.jpg)
Overall Survival
• Results could not be pooled d/t heterogeneity.
• No clear evidence on OS improvement by adding RT.
Toxicity • Results could not be pooled d/t differences
in reporting.
• RT appeared to be well tolerated.
![Page 13: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/13.jpg)
Summary
• RT prolongs PFS, with no impact on OS.
• RT must be considered an option for patients who cannot tolerate high dose or prolonged schedule of CTx.
![Page 14: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/14.jpg)
Advanced stage DLBCL: Pre-Retuximab Era
• Aviles (Mexico), RCT, 1994
• Ferreri (Italy), Retrospective, 2000
• Schlembach (MDACC), Retrospective, 2000
• Aviles (Mexico), RCT, 2004
![Page 15: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/15.jpg)
Ferreri et al. (Retrospective, 2000)
94 patients Tx arms Results p
Median 58 yrs Stage III/IV (31%/69%) •Bulky (≥10cm): 40% •Semibulky (6-9cm): 60%
CR after CHOP-like CTx RT or no RT <RT dose> - EF: med 38 Gy - IF: med 40 Gy
<Bulky> Med TTR: 41+ vs 18 m 5-yr OS: 73% vs 57% <Semi-bulky> Med TTR: 26+ vs 20 m 5-yr OS: 59% vs 41%
0.05 0.05 0.01 0.09
• Prolonged TTR and improved 5-yr OS by RT:
• Dose ≥36 Gy was related to longer OS.
• IFRT and EFRT were similar.
• No Tx-related death.
• No RT-related 2nd malignancy. Oncology 2000;58:219–226
![Page 16: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/16.jpg)
Aviles et al. (RCT, 2004)
341 patients Tx arms Results p
Median 53-57 yrs Stage IV Bulky Dz: ≥ 10 cm Clinical risk: high, high intermediate
CTx CR: Randomized: RT (40 Gy) (N=168) Obs (N=173)
5-yr EFS: 82% vs. 55% 5-yr OS: 87% vs. 66%
0.01 0.01
• More frequent relapse at initial site in Obs arm (63%) than in RT arm (7%).
• RT was well-tolerated with acceptable toxicity.
• RT improved EFS and OS in Pts with worse prognostic factors. RT should be part of initial Tx in this setting.
Leuk Lymphoma 2004;45:1385-1389
![Page 17: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/17.jpg)
Post-Retuximab Era
• Retrospective experiences: MDACC; Duke
• RICOVER-60 vs RICOVER-NoRTh
• UNFOLDER trial – interim analysis
![Page 18: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/18.jpg)
469 DLBCL Pts treated at MDACC (Jan 2001~Dec 2007)
Pts with CR RT (30-39.6 Gy) Pts with PR salvage CTx
![Page 19: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/19.jpg)
Longer OS/PFS by matched-pair analyses: • Pt who received 6-8 cycles of R-CHOP ± RT • 3 factors: bulky status, response, IPI score • 44 pairs in stage I/II, 74 pairs in stage I~IV
![Page 20: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/20.jpg)
• No in-field failure in Pts receiving RT!
Stage + RT - RT p
5-Y OS I/II 92% 73% 0.0007
III/IV 89% 66% 0.008
5-Y PFS I/II 82% 68% 0.003
III/IV 76% 55% 0.003
![Page 21: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/21.jpg)
Summary of MDACC Data
• Lessons from 4 randomized trials:
– RT achieved LC at original disease site when used with Abb-CTx.
– Abb-CTx failed to control disease at distant sites and was responsible for inferior outcome.
• Bulky disease did not affect outcome in relation to RT:
– All Pts (± bulky Dz) benefited from RT.
– This signifies importance of RT as complementary to CTx.
![Page 22: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/22.jpg)
• 79 stage III-IV DLBCL (1991 to 2009)
• CR following med #6 CTx: R-CHOP (65%); CHOP (22%); other (13%)
• Consol ISRT (med 25 Gy) in 38 (48%) Pts.
![Page 23: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/23.jpg)
Summary of Duke Data
• Improved in-field control (92% vs. 69%, p=0.028) and EFS (85% vs. 65%, p=0.014)
• No OS difference (85% vs. 78%, p=0.15)
• Pts with stage III-IV DLBCL who achieve CR on post-CTx imaging have improved in-field control and EFS with low-dose consolidation RT.
![Page 24: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/24.jpg)
![Page 25: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/25.jpg)
Between January 2001 and June 2004 124 CR Pts after R-CHOP14 IFRT (30 Gy) vs. Obs “Closed prematurely” Acute toxicity was mild and well tolerated. IFRT in mediastinal B-cell lymphoma who achieved CR remain as the best.
10-year PFS 10-year OS
IFRT (N=63) 72% 72%
Obs (N=61) 20% 31%
p <0.001 <0.001
Incredible?!
![Page 26: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/26.jpg)
• Best arm of RICOVER-60 trial (N=117) vs RICOVER-noRTh (N=47) in Pts with bulky Dz: #6 R-CHOP-14+2R ± IFRT (36 Gy)
![Page 27: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/27.jpg)
Additive RT to bulky sites abrogates bulky disease as a risk factor and improves outcome of elderly patients with aggressive B-cell lymphoma.
ITT Per protocol
![Page 28: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/28.jpg)
![Page 29: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/29.jpg)
Optimal RT Volume & Dose?
• SMC Data, 2010
• BCCA Data, 2012
![Page 30: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/30.jpg)
• 86 Pts with stage I/II H&N DLBCL
– CHOP-based CTx + ILRT
• 38-54 Gy (median 41.4 Gy) in 1.8 or 2.0 Gy/ fx (daily)
– Mostly 40-45 Gy (for 94.2%)
• ILRT = similar to INRT in Hodgkin lymphoma
CTV: Pre-CTx gross tumor with 1 cm margin
– Restricted by post-CTx anatomic limits
– Total margin from CTV to field edge was 1~2 cm
IJROBP 2010
![Page 31: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/31.jpg)
IJROBP 2010
• Pts with stage I/II H&N DLBCL did not need whole-neck
irradiation.
• ILRT might reduce RT toxicity with favorable outcomes.
![Page 32: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/32.jpg)
• Limited stage DLBCL (Stage IA/IIA, non-bulky Dz)
• #3 CHOP or CHOP-like CTx and RT
• 1981~1996: IFRT (N=138)
• 1996~2007: INRT ≤ 5cm (Pre-CTx volume + ≤5 cm)
(N=150)
Optimal RT field
Cancer 2012
![Page 33: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/33.jpg)
Cancer 2012
![Page 34: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/34.jpg)
Cancer 2012
![Page 35: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/35.jpg)
![Page 36: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/36.jpg)
![Page 37: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/37.jpg)
Toxicity Issue
• Significant dose-related cardiac toxicity by Doxorubicin-based CTx.
(Hershman et al, JCO 2008)
• Reduced cardiac toxicity by less CTx in CMT.
(Pugh et al, IJROBP 2010)
• No increased 2nd cancer risk by additional RT in large cohort studies.
(Mudie et al, JCO 2006, Tward et al, Cancer 2006, Sacchi et al Haematologica 2008)
![Page 38: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/38.jpg)
![Page 39: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/39.jpg)
When will RT exert the most benefit?
• Dz distribution is restricted to site(s) that can be encompassed in a contiguous limited RT field.
• RT can reduce need for long intensive and more toxic CTx.
• Elderly Pts (poor tolerance, limited salvage options)
• Bulky Dz or extranodal disease
• Sub-optimal response to CTx (PET positive or ?)
• Special sanctuary sites (testis, CNS)
![Page 40: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/40.jpg)
![Page 41: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/41.jpg)
![Page 42: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/42.jpg)
![Page 43: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/43.jpg)
![Page 44: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/44.jpg)
![Page 45: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/45.jpg)
![Page 46: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/46.jpg)
![Page 47: Role of RT in aggressive NHL 1406](https://reader030.fdocuments.us/reader030/viewer/2022020207/5563cae7d8b42a054f8b4eae/html5/thumbnails/47.jpg)