comparison of sib-imrt and conventional accelerated hyper-fractionated imrt with concurrent...
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Comparison of SIB-IMRT and Conventional Accelerated Hy
per-fractionated IMRT With Concurrent Cisplatin and Etop
oside for Limited Disease SCLC
Baosheng Li M.D. Ph.D.
Shandong Cancer Hospital,
Department of Radiation Oncology
Disclosure
No conflict of interests to disclosure
Background
At the time of diagnosis, 30%-40% of SCLC patients present with limited disease (LD).
SCLC is characterized by a rapid doubling time,high growth fraction, and early development of widespread metastases.
Patients with disease in excess of T1-2, N0 do not benefit from surgery.
Concurrent chemoradiotherapy represents the standard treatment for patients with LD-SCLC.
Background
Accelerated hyper-fractionated radiotherapy (4
5Gy with 1.5Gy twice daily in 3 weeks)
Dose-escalated conventional radiotherapy (60-70
Gy with 2Gy once daily in 6 to 7 weeks )
Concurrent chemoradiotherapy have been docu
mented as reliable schedules.
RT in SCLC
53.6%±3.3% SCLC patients need RT in every stage in the disease
45.4%±4.3% SCLC patients in the initial treatment
8.2%±1.5% SCLC patients later for recurrence or progression
Local failures occur in approximately one third of patients and the outcome is still poor.
RTOG 97-12
Komaki R, et al. IJROBP. 62,342-350, 2005
Lg Field (1.8 Gy/Fx) Boost (1.8Gy Bid) Total Dose
x (off cord)
RTOG 97-12
Wk 1 2 3 4 5
RTOG 0239
RT compliance rate: 95 %
Objective response:
CR: 41%, PR: 39%
2Y OS: 36.6 %
Severe hematopoietic toxicity was
as high as 90% ( 15 grade 3 and 49
grade 4).
Protocol: 6 cycles of etoposide and cisplatin .
Cycles 4 and 5 included concurrent higher dose
TRT (30Gy/20 twice daily fractions, a 2-week b
reak, and another 30Gy/20 twice daily fractions).
NCCTG 95-20-53
Schild SE,et al. J Clin Oncol 2007, 25: 3124-3129.
Results
A total of 76 assessable patients enrolled.
5-year OS rate: 24%.
The locoregional failure remained a proble
m and grade 3 or grade (3+) toxicities were
as high as 97%.
Phase III trial of concurrent thoracic radiotherapy wit
h either first- or third-cycle chemotherapy for limited-d
isease small-cell lung cancer
Sun jm,et al. Ann Oncol. 2013;24(8):2088-92
Results: 222 patients were randomly assigned
early TRT Late TRT P-value
CR 36% 38% >0.05
Median OS 24.1 26.8 >0.05
Median PFS 12.4 11.2 >0.05
Meutropenic fever 21.6% 10.2% 0.02
Conclusion: TRT starting in the third cycle of chemotherapy seemed to be
noninferior to early TRT, and had a more favorable profile with regard to ne
utropenic fever.
Our retrospective study was to compare toxicitie
s, disease control and survival outcomes for LD-
SCLC treated with simultaneous integrated boos
t intensity-modulated radiation therapy (SIB-IM
RT) versus conventional accelerated hyper-fracti
onated radiotherapy.
Purpose
METHODS
Group AGroup A Group BGroup B TotalTotal PP**Number of patientsNumber of patients 4343 5757 100100 Age (years)Age (years) 0.0780.078
mediamediann
5555 5757 5656
rangerange 35-7235-72 40-7440-74 35-7435-74
ECOG PS ECOG PS 0.4600.460 0-10-1 4141 5151 9292 22 22 66 88GenderGender 0.1300.130 MM 2929 4646 7575 FF 1414 1111 2525 AJCC 7 stage AJCC 7 stage 0.9400.940 ⅠⅠ 11 11 22 ⅡⅡ 55 88 1111 ⅢⅢAA 1414 2727 3131 ⅢⅢBB 1515 2121 2929
Patient Patient CharacteristicCharacteristicss
Chemotherapy
Two cycles chemotherapy before TRT with EP regi
men (etoposide 100mg/m2 day 1-5, and cisplatin 25
mg/m2 day 1-3, 21 days per cycle) were delivered.
Then adjuvant chemotherapy were administered af
ter completion of thoracic radiotherapy. Chemothera
py was administered every 3 weeks.
A total of 4-6 cycles were administered.
GTV: including the residual primary tumor and involve
d lymph nodes after induction chemotherapy.
TDF: 1.9Gy/f @ 30f in 3 weeks, 5 days a week.
CTV: defined by expanding GTV with a 0.5 cm margin
and involved lymph node region.
TDF: 1.7Gy/f @ 30f in 3 weeks , 5 days a week.
PTV: defined by expanding CTV with a 0.5 cm margin.
TDF: 1.5Gy/f @ 30f in 3 weeks , 5 days a week.
SIB-IMRT protocols
SIB-IMRT
The targets were defined as the same as SIB-IMRT.
TDF:1.5Gy/f @ 30f in 3 weeks , 5 days a week to PTV.
Conventional Accelerated Hyper-fractionated Radiotherapy Protocols
Lung : mean lung dose < 20Gy, lung V20 < 33
% ;spinal cord : Dmax≤41Gy;
Heart : mean heart dose < 30Gy , V40<46% ; Esophagus : mean esophagus dose < 34 Gy,
V35 < 50% .
Organs at risk
Patients who achieved CR or nCR were ad
ministered PCI (25 Gy in 10 fractions to the en
tire brain) within 4 weeks after completion of a
ll chemotherapy.
Prophylactic cranial irradiation
Results
Group A Group B
mean ± SD mean ± SD P*
MLD(Gy)a 17.7 ± 10.3 14.8 ± 1.7 0.099V5(%)b 67.4 ± 9.0 66.4 ± 9.8 0.678
V15(%)b 37.8 ± 5.8 36.3 ± 7.8 0.188V20(%)b 28.7 ± 3.2 24.5 ± 4.6 0.272V25(%)b 20.8 ± 4.4 19.0 ± 3.8 0.604V30(%)b 17.1 ± 2.6 14.1 ± 2.6 1.000V35(%)b 12.6 ± 3.5 11.3 ± 2.8 0.534
Ipsilateral lungs MLD(Gy) 22.1 ± 4.1 20.9 ± 3.5 0.564
V5(%) 79.1 ± 10.7 79.1 ± 11.7 0.941V15(%) 61.1 ± 11.7 61.2 ± 10.7 0.633V20(%) 47.2 ± 11.3 45.6 ± 9.3 0.536V25(%) 37.7 ± 11.2 34.3 ± 8.8 0.472V30(%) 30.3 ± 10.0 27.7 ± 8.5 0.761V35(%) 24.1 ± 8.6 22.0 ± 10.1 0.717
Contralateral lungs MLD(Gy) 8.8 ± 2.9 8.1 ± 2.9 0.773
V5(%) 53.1 ± 13.1 55.0 ± 12.8 0.962V15(%) 18.6 ± 10.1 15.8 ± 11.6 0.748
Total lungsTotal lungs
V20(%) 11.8 ± 8.8 7.3 ± 7.3 0.567
V25(%) 7.2 ± 5.5 4.5 ± 4.8 0.512
V30(%) 5.2 ± 4.6 3.3 ± 3.6 0.457
V35(%) 3.6 ± 3.4 2.2 ± 2.5 0.415
Spinal cord Dmax(Gy)e 42.7 ± 3.7 41.0 ± 1.2 0.090
Heart
Dmean(Gy)a 16.1 ± 7.3 15.0 ± 7.2 0.641
V30(%)c 23.3 ± 15.0 18.1 ± 11.4 0.253
V40(%)c 9.0 ± 5.0 6.7 ± 3.8 0.342
Esophagus
MED(Gy)a 29.0 ± 6.7 26.8 ± 5.5 0.575
V45(%)d 33.6 ± 5.3 33.0 ± 4.5 0.882
Toxicity
Toxicity Grade A组 B组 Total P*
Hematologic toxicit(WBC )
≥2 38 (88%)
30 (53%)
68 (68%) <0.001
Hematologic toxicity( PLT )
≥2 9 (21%) 9 (16%) 18 (18%) 0.508
Hematologic toxicity( HB )
≥2 11 (26%)
11 (19%)
22 (22%) 0.453
Stomach/intestine ≥2 16 (37%)
12 (21%)
28 (28%) 0.075
Esophagitis ≥2 23 (53%)
26 (46%)
49 (49%) 0.435
Pneumonitis ≥2 5 (11%) 3 (5%) 8 (8%) 0.284
Treatment response
Results Group A
N = 43
Group B
N = 57
P*
0.953
Response
Complete response 22 (51%) 28 (49%)
Partical response 16 (37%) 20 (36%)
Near complete response 5 (11%) 5 (8%)
Total 38 (88%) 48 (85%)
Stable disease 4 (9%) 6 (10%)
Progressive disease 1 (3%) 3 (5%)
SurvivalOutcome measure Group A Group B P*
Overall survival 0.165
Median duration 32months 28months
2 Years 70.2% 55.2%
3 Years 46.3% 36.2%
Progression-free survival 0.077
Median duration 22.5months 15.5monts
2 Years 45.7% 35.9%
3 Years 30.1% 18.6%
Locoregional recurrence-free survival 0.093
Median duration 31.5months 23monts
2 Years 67.3% 46.8%
3 Years 34.9% 26.3%
OS
P = 0.165
PFS
P = 0.077
LRFS
P = 0.093
Conclusions
Comparing with conventional accelerated hyper-
fractionated RT, SIB-IMRT for limited Disease S
CLC was feasible and had the potency of
improving local regional recurrence. However, the
toxicity was still higher.
Acknowledgements
• Dr. Dan Han
• Dr. Tao Zhou
• Dr. Zhongtang Wang
• Dr. Hongsheng Li
• Prof. Yong Yin
• Associate Prof. Jian zhu
Thank you !