Quantitative Dosimetric Analysis Of Patterns Of Local Relapse After IMRT For Primary Extremity Soft Tissue Sarcomas

Ryan M. Lanning, Sean L. Berry, Michael R. Folkert, and Kaled M. Alektiar

Dept. of Radiation Oncology and Medical PhysicsMemorial Sloan-Kettering Cancer Center

Disclosures

• We have no conflicts of interest to disclose.

Characterizing Local Recurrence

Marginal

Central

Distant

Scar

RT Field

Objectives

• Characterize local recurrence of extremity STS treated with adjuvant IMRT based on dose received to the recurrence volume.

• Determine any patient, tumor, or treatment characteristics that may predict local recurrence.

Soft Tissue Sarcoma Study Population

Time Period: 2/2002 – 12/2010# of patients: 165Male: 101 (61%)Female: 64 (39%)Median Age: 55 (19-88) years

Pre-op IMRT: 34 (21%)Median: 50Gy (48-50)

Post-op IMRT: 131 (79%)Median: 63Gy (27-66.6)

Tumor and Treatment Characteristics

% nTumor Size: >10 cm 44% 73Grade: High 87% 143Depth: Deep 91% 150Site: Lower extremity 74% 123Margin Status: Positive / Close 52% 85Adjuvant Chemo: Yes 27% 45

Original RT Fields and LR Patterns

Recurrence Based on Dose Distribution

Recurrence

CTVPTV

Dosimetric Characterization of Recurrence

0 20 40 60 80 100 1200

102030405060708090

100110

Marginal Central

Dose (% Prescription)

Volu

me

(%)

V95

Relationship to 95% IDL*

Central =Completely

within

Marginal =Crosses

Distant =Completely

outside

* : Milano MT et al. IJROBP 2010

Outcomes

n % 5-yr LR Median time to LR (mo)

Overall 13 -8.4%

(95% CI: 3.8 - 13)19

(range: 9 - 61)

Central 4 312.9%

(95% CI: 0 - 5.7)24

(range: 13 - 28)

Marginal 8 615.0%

(95% CI: 1.4 - 8.6)18

(range: 9 - 61)

Distant 1 8 0.7%(95% CI: 0 – 2.1)

19

Median Follow-up = 42 months

Predictors of Local RecurrenceFactor Events 5-yr LR (%) P-value

Age 50 yrs 2 / 54 4

0.19> 50 yrs 11 / 111 10

Size 10cm 5 / 92 5 0.12> 10 cm 8 / 73 13

Margin Negative 4 / 80 4 0.18Positive / close 9 / 85 12IMRT

SchedulingPreop 4 / 34 15

0.24Postop 9 / 131 7

Histology

Liposarcoma 2 / 50 5

0.41MFH 4 / 35 13

Myxofibrosarcoma 4 / 33 13Other 3 / 46 6

Depth: p = 0.24 Chemo: p = 0.66Site: p = 0.75 Grade: p = 0.95

Conclusions• Dosimetric analysis provides a quantitative

tool for characterizing local recurrence• Traditional predictors of local recurrence in

STS appear to exert less influence in the setting of IMRT

Tumor Biology

Treatment

Acknowledgements

• My collaborators: Dr. Sean Berry and Dr. Michael Folkert

• My mentor: Dr. Kaled Alektiar• CTOS selection committee, Committee chairs,

and our discussant

Room for Improvement?Histology Site dMax

(cm) Grade Margin IMRT Vrecur 95% IDL LR

1 Liposarcoma Thigh 25 Low Close / + Post-op 100% Central2 Liposarcoma Thigh 18 High Close / + Post-op 100% Central3 Myxofibrosarcoma Thigh 10.5 High Close / + Post-op 100% Central4 Myxofibrosarcoma Hand 1.6 High Close / + Pre-op 100% Central5 MFH Thigh 12 High Close / + Post-op 94.4% Marginal6 MFH Thigh 15 High Negative Post-op 93.6% Marginal7 MFH Thigh 15.3 High Negative Post-op 92.3% Marginal8 STS (NOS) Arm 6.5 Low Negative Post-op 90.5% Marginal9 STS (NOS) Thigh 5.1 High Close / + Post-op 74.1% Marginal10 Fibrosarcoma Triceps 8 High Close / + Pre-op 35.3% Marginal11 Myxofibrosarcoma Thigh 21 High Close / + Pre-op 18.5% Marginal12 Myxofibrosarcoma Thigh 17.9 High Negative Post-op 0.1% Marginal13 MFH Knee 6.6 High Close / + Pre-op 0% Distant

Recurrence CharacteristicsHistology LR Site LR

ConfirmationTime LR

to MRI (d)Vrecur

(cc) Salvage

1 Liposarcoma Central Clinical 0 23.2 S2 Liposarcoma Central Biopsy 10 48.2 S/B3 Myxofibrosarcoma Central Clinical 0 5.1 C/S/B4 Myxofibrosarcoma Central Biopsy -37 1.2 S5 MFH Marginal Biopsy 1 27.6 S6 MFH Marginal Clinical 0 32.0 C7 MFH Marginal Clinical 0 67.3 C8 STS (NOS) Marginal Biopsy 0 53.0 S9 STS (NOS) Marginal Biopsy -15 7.6 R/S10 Fibrosarcoma Marginal Biopsy 4 36.0 S11 Myxofibrosarcoma Marginal Clinical 0 47.7 S/C12 Myxofibrosarcoma Marginal Biopsy -1 737.8 R/S13 MFH Distant Biopsy -14 132.4 None

S = Surgery C = Chemotherapy R = EBRT B = Brachytherapy

CTV: GTV + 1-1.5 cm in radial axis

PTV: CTV plus 1 cm margin in all directions

Volume Expansion: Pre-op IMRTCT

V: G

TV +

4 c

m in

long

axi

s

CTV

: Tum

or b

ed +

4 c

m in

long

axi

s

PTV: CTV plus 1 cm margin in all directions

CTV: Tumor bed + 1-1.5 cm in radial axis

Volume Expansion: Postop IMRT

Local Recurrence: EBRT vs IMRT

• Competing risks, cumulative incidence, Gray’s test and Fine and Gray regression were used to estimate 5-y local recurrence:

– IMRT:7.6% (95% CI 3.4-11.8%)

– Conventional EBRT: 15% (95% CI 9.2-20.9%)

P = 0.049

Courtesy of MR Folkert

Discussion points – Basis of Improved Outcome?

• Improved conformality and homogeneity of dose may be the basis of improved local control.

1. Swanson EL et al, Int J Radiation Oncology Biol Phys. 2012 83(5):1549-57. 2. Stewart AJ et al, Radiother Oncol. 2009 Oct;93(1):125-30.3. Griffin AM et al, Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):847-56.

Conformity/ConformalityHomogeneity/Heterogeneity

Study IMRTConventional

EBRT IMRTConventional

EBRTSwanson et al1 0.75 0.51 0.066 0.073Stewart et al2 1.33-1.59 1.76 1.036-1.045 1.052

Griffin et al3 1.27 1.76-2.34 n/a n/a

Courtesy of MR Folkert

Predictors of Local RecurrenceFactor Events 5-yr LR (%) 95% CI P-value

Age 50 yrs 2/54 4 1 - 7

0.19> 50 yrs 11/111 10 7 - 14

Site Upper 3/42 6 2 - 10 0.75Lower 10/123 9 6 - 12

Size 10cm 5/92 5 2 - 8 0.12> 10 cm 8/73 13 8 - 17

Grade Low 2/22 5 0 - 9 0.95High 11/143 9 6 - 12

Margin Negative 4/80 4 2 - 6 0.18Positive / close 9/85 12 8 - 16IMRT

SchedulingPreop 4/34 15 8 - 22 0.24Postop 9/131 7 4 - 9

Histology

Liposarcoma 2/50 5 1 - 8

0.41MFH 4/35 13 7 - 19

Myxofibrosarcoma 4/33 13 7 - 18Other 3/46 6 2 - 11

Depth: p = 0.24 Chemo: p = 0.66