Malignancy Grade and Histologic Subtype of Primary Retroperitoneal Sarcoma (RPS) are Predictive of...
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Transcript of Malignancy Grade and Histologic Subtype of Primary Retroperitoneal Sarcoma (RPS) are Predictive of...
Malignancy Grade and Histologic Subtype of Primary Retroperitoneal Sarcoma (RPS) are Predictive of Pattern
of Recurrence: a Large Retrospective Study from the Transatlantic RPS Working Group
Gronchi A, Strauss D, Miceli R, Bonvalot S, Swallow CJ, Hohenberger P, Van Coevorden F, Rutkowski P, Callegaro D,
Pollock RE and Raut CP
Disclosures
• No disclosures
Background
Surgery is the primary and only curative treatment of localized disease
Quality of local treatments and biology of the tumor are the major determinants of outcome
Gronchi A and Pollock RE. Ann Surg Oncol 2013; 20(7): 2011-2013
ControversyWhat is the appropriate extent of resection?
Great Debates SSO 2013
Toulemond et al. Ann Oncol 2014; 25: 735-742
Questions
• What are the patterns of recurrence and survival?
• Do different strategies by institution translate into different outcomes?
Methods
Trans-Atlantic RPS Working Group
• 1007 consecutive primary adult-type RPS from 8 centers– Ewing/PNET, alveolar/embryonal rhabdo, desmoid,
GYN sarcoma and GIST excluded
Patient Characteristics• 2002-2011
• M 52%, F 48%
• Median age: 58 (IQR 48-67)
• Median size: 20 cm (IQR 13-30 cm)
• Macroscopic complete resection: 95%– Tumor rupture with spillage in the operative field: 6%– Contamination: 4%
• Multifocality: 9%
• Distance from home > 100km (62 miles): 46%
Patient Characteristics• Postoperative complication ≥3 according to CTCAE: 21%
• Reoperation: 11%
• Median number of resected organs: 2 (IQR 1-4)
• CT done: 18% (Anthracyclin based: 12%)
• RT done: 32% (preoperatory: 20%)
• Median FU: 58 months (IQR 36-90)
• Grading: 1 (34%), 2 (38%), 3 (28%)
WD LPSGII DD LPSGIII DD LPSLEIOSFTMPNSTUPSOTHER
Histology Distribution
Statistical Analysis
• OS estimated with KM curves
• CCI of LR and DM calculated in a competing risk framework
• Multivariable Cox regression analysis of OS, LR and DM
Results
Over
Entire Cohort
5-yr 66.8% (95%CI 63.5-70.2%)8-yr 56.1% (95%CI 52.0-60.6%)10-yr 45.8% (95%CI 39.7-52.8%)
5-yr CCI 25.9% (95% CI 23.1-29.1%)8-yr CCI 31.3% (95%CI 27.8-35.1%)10-yr CCI 35.0% (95%CI 30.5-40.1%)
5-yr CCI 21.0% (95% CI 18.4-23.8%)8-yr CCI 21.6% (95%CI 19.0-24.6%)10-yr CCI 21.6% (95%CI 19.0-24.6%)
0.0
0.1
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0.5
Time (months)
CC
I
0 12 24 36 48 60 72 84 96
0.0
0.1
0.2
0.3
0.4
0.5
Time (months)
CC
I
0 12 24 36 48 60 72 84 96
Time (months)
OS
0 12 24 36 48 60 72 84 96
0.0
0.2
0.4
0.6
0.8
1.0
Overall Survival
Local Recurrence Distant Metastasis
Current status – overall survival
SEER: Primary 1365 RPS5yr OS – 47% (2010)
Time (months)
OS
0 12 24 36 48 60 72 84 96
0.0
0.2
0.4
0.6
0.8
1.0
Transatlantic Sarcoma Group>1000 Primary RPS
5yr OS – 67% (2014)
OS by Histology
WD LPS: 83.4%
SFT: 76.5%
GIII DD LPS: 30.2%
LMS: 43.4%
GII DD LPS: 51.1%
0.0
0.1
0.2
0.3
0.4
0.5
Time (months)
CC
I
LMS 1MPNST 1Other 1SFT 1UPS 1WD-lipo 1DD-lipo-G1-2 1DD-lipo-G3 1
0 12 24 36 48 60 72 84 96
WD LPS: 34.5%
SFT: 14.0%
GIII DD LPS : 38.0%
LMS: 11.6%
GII DD LPS: 49.1%
LR by Histology
0.0
0.1
0.2
0.3
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0.5
Time (months)
CC
I
LMS 2MPNST 2Other 2SFT 2UPS 2WD-lipo 2DD-lipo-G1-2 2DD-lipo-G3 2
0 12 24 36 48 60 72 84 96
DM by Histology
WD LPS: 0.4%
SFT: 12.7%
GIII DD LPS: 32.6%
LMS: 52.6%
GII DD LPS: 9.1%
Results from the Cox proportional hazards models on the three endpoints analyzed. OS LR DM HR 95% CI P HR 95% CI P HR 95% CI PAge, years <0.001 0.004 0.055 67 vs. 48* 1.49 (1.25, 1.77) 1.27 (1.07, 1.50) 1.21 (1.00, 1.47) Size, cm 0.021 0.115 0.090 30 vs. 13* 1.28 (0.99, 1.66) 1.31 (1.00, 1.71) 0.94 (0.71, 1.25) Surgical resection <0.001 <0.001 0.059 Incomplete vs. complete 2.54 (1.61, 4.00) 3.71 (2.35, 5.83) 2.02 (0.97, 4.17) FNCLCC grade <0.001 <0.001 <0.001 II vs. I 2.50 (1.44, 4.34) 2.54 (1.52, 4.25) 2.21 (1.26, 3.87) Multifocality <0.001 <0.001 0.003 Yes vs.no 1.91 (1.34-2.74) 2.16 (1.51-3.09) 1.93 (1.25-2.96)Histological subtype 0.076 0.009 <0.001 WD liposarcoma vs. SFT 1.65 (0.44, 6.18) 2.35 (1.04, 5.32) 0.53 (0.20-1.37) DD liposarcoma vs. SFT 1.64 (0.80, 3.35) 1.98 (0.92, 4.24) 0.98 (0.45, 2.13) Leiomyosarcoma vs.SFT 1.98 (0.95, 4.11) 1.06 (0.47, 2.40) 2.62 (1.22, 5.61) MPNST vs. SFT 1.69 (0.68, 4.19) 1.08 (0.38, 3.04) 0.93 (0.32, 2.70) Other vs. SFT 2.87 (1.31, 6.29) 1.67 (0.67, 4.15) 2.19 (0.95, 5.03) CT 0.208 0.175 0.429 Yes vs.no 1.21 (0.90, 1.64) 1.28 (0.90, 1.83) 1.14 (0.82, 1.59) RT 0.704 0.001 0.200 Yes vs. no 0.95 (0.71, 1.26) 0.55 (0.40, 0.77) 0.82 (0.60, 1.11)
Abbreviations: HR, hazard ratio; CI, confidence interval; OS, overall survival; LR, local recurrence; DM, distant metastases; WD: well differentiated; DD: dedifferentiated; SFT, solitary fibrous tumor; MPNST, malignant peripheral nerve sheath tumor; RT, radiation therapy; CT, chemotherapy.* The two values are, respectively, the 3rd and 1st quartiles of the variable distribution.
Should the strategy be tailored to histology subtype?
• Extended resection and/or radiation for GII-GIII DD LPS?
• Adjacent uninvolved organ preservation in LMS and SFT?
• WD LPS ?
A closer look at outcome by center
• specific center was not significant on multivariate analysis
but
some differences in strategy and outcomes were observed
1007 consecutive primary adult-type RPS from 8 centers
25%25%14 %
10 %12 %
14 %
1. Focus on WD LiposarcomaPure ALT Sclerosing, inflammatory, myxoid like, cellular
(GI DD)
1. Focus on WD Liposarcoma
tumor size by center number of resected organs by center
Boston London Milano Other Paris Toronto
02
46
810
N. r
esec
ted
orga
ns
Histotype: WD lipo
Abbreviations: IQR, interquartile range
5 (IQR 3-7)
3 (IQR 2-5)
2 (IQR 1-3)
Boston London Milano Other Paris Toronto
020
4060
80
Tum
or s
ize
(cm
)
Histotype: WD lipo
Abbreviations: IQR, interquartile range
26cm(IQR 14-24cm)
26cm(IQR 19-32cm)
24cm(IQR 16-33cm)
1. Focus on WD Liposarcoma
RT administration by center
No 100% 86,5% 28%
Yes 0% 13,5% 72%
Quality of surgery by center
Complete 100% 94% 100%
Incomplete 0% 6% 0%
0.0
0.1
0.2
0.3
0.4
0.5
Time (months)
CC
I
0 12 24 36 48 60 72 84 96
CCI of LR by center
5%
35%
50%
1. Focus on WD Liposarcoma
1. Focus on WD Liposarcoma
Time (months)
OS
0 12 24 36 48 60 72 84 96
0.0
0.2
0.4
0.6
0.8
1.0 88%
76%
88%
1. Focus on WD Liposarcoma
• Better local control in patients treated by extended resection and RT
• OS apparently unaffected at 8-yr time point
• LR risk seems to flatten out with a combination of extended surgery and RT
2. Focus on Leiomyosarcoma
tumor size by center number of resected organs by center
2. Focus on Leiomyosarcoma
Boston London Milano Other Paris Toronto
020
4060
80
Tum
or s
ize
(cm
)
Histotype: LMS
Boston London Milano Other Paris Toronto
02
46
810
N. r
esec
ted
orga
ns
Histotype: LMS
4 (IQR 3-4)
3 (IQR 2-3)
1 (IQR 0-2)
RT administration by center CT administration by center
2. Focus on Leiomyosarcoma
No 87% 66% 19%
Yes 13% 34% 81%
No 100% 37% 76%
Yes 0% 63% 24%
CCI of LR by center CCI of DM by center
2. Focus on Leiomyosarcoma0.
00.
10.
20.
30.
40.
50.
60.
7
Time (months)
CC
I
0 12 24 36 48 60 72 84 96
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Time (months)
CC
I
0 12 24 36 48 60 72 84 96
CCI of LR at 5yr7,4% 9,1% 0%
CCI of DM at 5yr38,9% 58,9% 55,9%
2. Focus on Leiomyosarcoma
• Optimal local control with adequate surgery + RT
• New therapies eagerly needed to address the systemic risk, as available ones seems not to help
Limitations
• Retrospective study
• Different case mix, different FU schedules
• No prospective QoL measures
• Similar surgical strategies, but different indication to adjuvant/neoadjuvant therapies
…in brief
After primary optimal surgery histology subtype is one of the major determinant of outcome
• G2-G3 DD LPS – highest LR rate
• G3 DD LPS and LMS – highest DM rate
• WD LPS indolent course but constant risk over time
• Conventional SFT – least LR and DM rate
Different strategies for local therapy
• May lead to different outcomes in low-intermediate grade LPS
125 over 256 patients recruited
Different strategies for local therapy
• May lead to different outcomes in low-intermediate grade LPS
• May be of limited value when the systemic risk is high (Leio, GIII DD LPS). Need new systemic agents to address the systemic risk
This unprecedented collaboration has led to:
• The collection of a large retrospective series which will serve as historical control for all future studies
• An open comparison of outcomes amongst participating centers, which allows to learn what are the best practice patterns at each institution.
• Active recruitment of the ongoing prospective randomized study on preoperative RT in RPS, which will answer to the question of the role of RT in this disease.
• Application for a prospective trans-atlantic registry to create a library of information to use for future therapies
Trans-Atlantic RPS Working Group