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 !

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