preoperative hypofractioned radiotherapy in localized extremity/trunk wall soft tissue sarcomas...
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PREOPERATIVE HYPOFRACTIONED RADIOTHERAPY IN LOCALIZED
EXTREMITY/TRUNK WALLSOFT TISSUE SARCOMAS
EARLY STUDY RESULTS
Hanna Kosela; Milena Kolodziejczyk; Tadeusz Morysinski; Wirginiusz Dziewirski; Marcin Zdzienicki; Piotr Rutkowski
Department of Soft Tissue/Bone Sarcoma and Melanoma, Department of Radiotherapy
Maria Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsaw, Poland
Background
Primary treatment of majority of localized soft tissue sarcoma is surgical resection of the tumor with adequate margins combined with radiotherapy
Using radiotherapy in the local setting increases local control of the disease (with suggested survival benefit for patients with high grade tumors*)
*Koshy M, et al. . Improved survival with radiation therapy in high-grade soft tissue sarcomas of the extremities: a SEER analysis. Int J Radiat Oncol Biol Phys. 2010 May 1;77(1):203-9
Background – preoperative radiotherapy vs postoperative setting
No differences in local recurrence rate, regional and distant failure rates*;*O'Sullivan B, et al. . Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.2002 Jun 29;359(9325):2235-41.
Benefits Drawbacks
• Lower doses and smaller treatment field size;
• Possible improvement in tumor resectability;
• Smaller incidence in long term radiation- related complications;
Increased risk of wound complications;
Background
Can we shorten the overall treatment time by using hypofractionated radiotherapy and immediate surgery in STS as in rectal carcinoma?
Potential benefits
• Lower risk of tumor clonogens repopulation
• Convenience
• Lower cost
Radiobiological rationale: low α/β ratio: -0,5-5 Gy*
*Gunderson LL, Tepper JE. Clinical Radiation Oncology. London, UK: ChurchillLivingstone; 2007
*
AIM OF THIS PILOT STUDY
Incidence of late complicatons and local recurrences compared to those observed after conventionally fractionated preoperative radiotherapy.
Overall survival;
Patients and methodsIn the years 2006-2010, 262 patients
received 5x5 Gy according to uniform internal preoperative protocol and underwent tumor resection within a consecutive week.
In our analysis we included only
patients with diagnosis of localized, resectable soft tissue sarcoma of the extremities or trunk wall (confirmed pathologically): primary or recurrent; deep seated and/or intermediate/high grade
Patients and methods
• 225 patients• 122 (54%) women, 103 (46%) men• Median age 54 years (range 18-82) • Median follow up 34 months (range 1-80)• Bioethical committee approval
Patients and methods
140 patients (62.2%)- primary tumors• 75 patients (33%) – clinical local recurrence after
previous surgery in another center• 10 patients (4.4%)- after non-radical surgery in
another center, but without clinical recurrence (scar)
56 (24.9%) patients received preoperative chemotherapy
75% of these patients had high grade tumors (G3)
Patients and methods
* 16 patients had also postoperative radiotherapy
Tumor size Median size 9cm (range 0,5-41cm)45%>10cm
Tumor grade 29- G1
54-G2
136- G3 (60%)
6- unknown
Final resection margin 176- R0 (78%)
41- R1*
2-R2
Results
• 51 (22.6%) patients were dead at the time of analysis
• 93 (41.3%) recurrences of the disease• 46 - local recurrence (20% local recurrence =
80% local control rate) - in 10 patients after local recurrence amputation was performed
• 78 (34.7%)- distant metastases• 31 (13.8%) patients had local and distant
recurrence of the disease
Overall survival (median - not reached)
0 10 20 30 40 50 60
T ime (months)
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
Survival probability
65%
~70%
L o ca l re cu rre n ce -fre e su rvi va l (m e d ia n - n o t re a ch e d )
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0 00 ,0 50 ,1 00 ,1 50 ,2 00 ,2 50 ,3 00 ,3 50 ,4 00 ,4 50 ,5 00 ,5 50 ,6 00 ,6 50 ,7 00 ,7 50 ,8 00 ,8 50 ,9 00 ,9 51 ,0 01 ,0 5
Pro
ba
bility o
f surviva
l
7 3 %
~80%
Factors influencing survival (univariate analysis)
OS:- Tumor size (p = 0.05)- Tumor grade (p = 0.0002)
LRFS:- Tumor grade (p = 0.007)
O v era ll surv iv a l according to tum or grade
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
G 1 +G 2 G 3
p =0 .0 0 0 2
Loca l recurrence-free surv iv a l according to tum or grade
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
G 1 +G 2 G 3
p =0 .0 0 7
O v era ll surv iv a l according to tum or s ize
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
<5 cm 5 -1 0 cm >1 0 cm
p=0.05
Loca l recurrence free surv iv a l according to tum or s ize
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
<5 cm 5 -1 0 >1 0 cm
p =0 .9
Ov erall s urv iv al ac c ording to tumor s tatus
0 12 24 36 48 60
Time (months )
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
Survival probability
Pr imary Sc ar af ter non-radic al ex c is ion Clin ic al rec urrenc e
p=0.9
Loc al rec urrenc e-f ree s urv iv al ac c ording to tumor s tatus
0 12 24 36 48 60
Time (months )
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
Survival probability
Pr imary Sc ar af ter non-radic al ex c is ion Clin ic al rec urrenc e
p=0.8
`~80%
~~60%
Loca l recurrence-free surv iv a l according to m argins of resec tion
0 1 2 2 4 3 6 4 8 6 0
T im e ( m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
R0 R1
p =0 .0 9
~75%
~~57%
O v era ll surv iv a l according to prim ary tum or s ite
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
Up p e r l im b T ru n k wa l l L o we r l im b
p =0 .1 4
Loca l recurrence free surv iv a l according to tum or s ite
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
p =0 .4 5
Up p e r l im b T ru n k L o we r l im b
O v era ll surv iv a l according to periopera tiv e chem otherapy
0 1 2 2 4 3 6 4 8 6 0
T im e (m o n th s)
0 ,0
0 ,1
0 ,2
0 ,3
0 ,4
0 ,5
0 ,6
0 ,7
0 ,8
0 ,9
1 ,0
Su
rvival p
rob
ab
ility
W i th p re o p ch e m o (n e o a d ju va n t) W i th o u t p re o p ch e m o
p =0 .1 2
Complications of the treatment
97 patients (43%) had postoperative wound complications including 9 patients (4%) who required an additional surgical procedure
33.6% of patients with complications received preoperative chemotherapy
87 patients with wound complications (89.6%) had tumor localized on the lower limb
Early local complications
• 38 (16.9%) patients had prolonged healing of the wound (>1 month)
• 28 (12.4%) patients had wound dehiscence• 9 (4%) patients required prolonged punctures of
the collecting lymph fluid• 6 (2.7%) patients had an increased acute skin
toxicity
Late complications
• 2 (0.8%) patients severe fibrosis leading to contracture of the limb
• 24 (10.7%) patients prolonged edema of the operated limb
• 6 (2.7%) patients - fracture of the treated limb (median time from treatment to fracture 18 months)
Conclusions
• Local control rates an overall survival similar to those seen in patients treated with preoperative radiotherapy conventionally fractionated;
• Our series comprises majority of high risk patients with large high grade tumors;
• Wound complication - quite high rate of early complications but low percentage of severe complications;
• Late complications - similar to those seen in patients treated with preoperative radiotherapy conventionally fractionated
• Cancer Center – Institute; Warsaw: K. Wiater, S. Falkowski, A. Klimczak, T. Świtaj, K. Ptaszyński,U. Grzesiakowska, E. Bylina, A, Głuszcz,…
• Our patients and their families
ACKNOWLEDGEMENTS