DOSE - Varian

varian

DOSE - Varian

Dose-time relationship

in stereotactic radiotherapy for

non-small cell lung cancer

Rafal Suwinski, Tomasz Dworzecki, Adam Idasiak


Background

• Stereotactic body radiotherapy (SBRT) is

gaining a rapidly increasing attention in

curative treatment for early stage non small

cell lung cancer (NSCLC).

• The fractionation schedules used in SBRT

were developed empirically, with more

recent attempts frequently based on RTOG

0236


Chest 2005, 124: 1946-1955

NSCLC, stage I, medically inoperable


3 � 20 Gy

OTT 1.5-2 weeks


LC 3-years: 88 %

RTOG 0236


Author No patients Total

dose

Dose per

fraction

No of

fractions

LRC Follow-up

Baumann 2009 57 45 Gy 15 Gy 3 92% 3 years

Nyman 2006 45 45 Gy 15 Gy 3 80% 4 years

Onishi 2004 35 60 Gy 6 Gy 10 94% 1 year

Ricardi 2009 62 45 Gy 15 Gy 3 88% 3 years

Stephans 2009 56

38

Timmermann

(RTOG 0236)

SBRT in NSCLC

50 Gy

60 Gy

10 Gy

20 Gy

5

3

97%

100%

1 year

1 year

56 60 Gy 20 3 98% 3 years

Takeda 2009 63 50 Gy 10 Gy 5 93% 3 years

Fakiris 2009 106 60 Gy 20 Gy 3 88% 3 years

Tung 2008 20 54 Gy 18 3 95% 2 years

Videtic 2009 26 50 Gy 10 Gy 5 94% 3 years

Xia 2006 43 70 Gy 7 Gy 10 95% 3 years


SBRT in Gliwice since 2002

Współczesna Onkologia 2005, 9: 257-262.


Gating, since 2006

Nowotwory, Journal of Oncology 2007, 57: 105-113


Purpose

• To analyze dose-time relationship and

clinical outcome of individuals with early

stage NSCLC treated in Center of Oncology

in Gliwice with SBRT, including the patients

treated with long overall treatment time

(according to present-day standards)


Clinical characteristics of patients

N: 44 patients

Gender: M: 35, F: 9

Age: median 71 years, range 48-90

Stage: stage I: 27 patients, stage II: 3 patients,

stage III 2 patients, stage IV 12 patients*

Nodes: 44 N0

* Patients with stage IV disease had small lung tumor with solitary brain metastasis that was surgically excised

or treated with stereotactic radiotherapy


Treatment parameters

Total dose: 20-45 Gy: 15 pts

46-54 Gy: 14 pts.

55-60 Gy: 15 pts.

Dose per fraction: 10-17 Gy: 10 pts.

18 Gy: 12 pts.

20 Gy: 20 pts.

24 Gy: 2 pts.

OTT: < 6 weeks (median 22 days) 34 pts.

>6 weeks (median 50 days) 10 pts.


NUMBER OF PTS.

18

16

14

12

10

8

6

4

2

0

TUMOR VOLUME

0,5-5 cm3

5-10 cm3

VOLUME (cm 3 )

5-50 cm3


LRC

1,0

0,8

0,6

0,4

0,2

Clinical outcome

0,0

0 1 2 3 4 5

TIME (YEARS)

Loco-regional control (44 pts.)


LRC

1,0

0,8

0,6

0,4

0,2

LRC vs. OTT

OTT > 6 weeks

p=0.01

0,0

0 1 2 3 4

TIME (YEARS)

OTT< 6 weeks


LRC

1,0

0,8

0,6

0,4

0,2

LRC vs. ZUBROD

ZUBROD 2

p


Variables that did not influence LRC

• Total dose

• Dose per fraction

• Clinical stage

• Age

• Gender


Biological dose (fraction dose)

LQED 2Gy=n* (α/β+d)/ (α/β+2)

N: number of fractions

D: dose per fraction


Biological dose (time effect)

LQED TIME=LQED 2Gy-γT

γ – dose increment to compensate

for an extension in OTT


Logistic analysis of dose-response

LRC=

data

exp[b1+(b2×dose)+(b3×time)]

1+exp[b1+(b2×dose)+(b3×time)]


LRC

1,0

0,8

0,6

0,4

0,2

0,0

Logistic analysis of dose-response data

OTT=14 DAYS

OTT=60 DAYS

0 20 40 60 80 100 120 140 160

DOSE (Gy)


Estimates of dose increments to

compensate for day extension in OTT

• 0,23 Gy (assuming α/β for tumor of 10 Gy)

• 0,74 Gy (assuming α/β for tumor of 100 Gy)

• 0,45 Gy (assuming α/β for tumor of 10 Gy and lag

period for tumor repopulation of 30 days)


LRC

1,0

0,8

0,6

0,4

0,2

LRC vs. LQED 2Gy

LQED2 TIME70 Gy

p=0.02


Conclusions

These data demonstrate that the estimates of

biologically equivalent radiation doses in SBRT must

incorporate the effect of overall radiation treatment

time, such as in conventionally fractionated

radiotherapy.

Unduly long overall treatment times that were

permissible in early attempts of SBRT in lung cancer

have to be avoided according to present day

experience.

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