1. An Assessment of Factors Affecting Outcome in Patients Presenting with Metastatic Soft Tissue Sarcoma
Peter Ferguson MD1,2, Benjamin Deheshi MD1,2, Anthony Griffin MSc1, Robert Bell MD1,2, Brian O’Sullivan MD3, Charles Catton MD3, Peter Chung MD3, Jay Wunder MD1,2
1 Musculoskeletal Oncology Unit, Mount Sinai Hospital
2 Department of Surgery, University of Toronto
3 Department of Radiation Oncology, Princess Margaret Hospital

2. 44 year old woman
Painful mass in paraspinal region
2 small pulmonary nodules
Bx – grade 3 leiomyosarcoma
Preop radiation

3. Mass grew on radiation
Patient unable to lie supine due to large mass and severe pain requiring narcotics
Chest x-ray at time of surgery…

4. Post op wound infection
Patient dead of progressive metastatic disease within 2 months

5. 60 year old male
Early onset Alzheimer’s, otherwise healthy
Rapidly growing mass left proximal thigh
Bedridden due to severe pain
Bx – grade 3 MFH

6. CT chest after radiation shows small pulmonary nodules
Patient underwent resection, free latissimus dorsi flap
Never regained ambulatory status
Dead of progressive metastatic disease within 3 months

7. 62 year old male
Rapidly growing right chest wall mass
Patient bedridden in severe pain
Required dressing changes several times per day
Repeated transfusions for anemia

8. Preop radiation
Resection and TRAM flap
Partial flap necrosis requiring dressing changes
Patient did not regain ambulatory status
Dead of progressive metastatic disease 2 months later

9. Rationale
What role does surgery play in treating patients presenting with primary metastatic STS?
Attempt at cure?
Prolong life?
Palliation of symptoms?

10. Rationale 5 year disease specific survival of AJCC stage IV STS – 6%
Can surgical resection be withheld from patients presenting with stage IV disease on this basis?
Is it possible to predict which patients are more likely to be cured and therefore benefit from aggressive surgical resection?
Is it possible to determine factors associated with longer survival?

11. Billingsley et al, Ann Surg, 229(5): p 602.
719 patients who either presented with or developed pulmonary mets
Predictors of outcome on Cox modelling – complete resection of pulmonary mets, disease free interval > 12 months, low grade sarcoma
No differentiation between those who presented with or developed mets

12. Casson et al, Cancer 69(3): p. 662.
Group of STS patients undergoing pulmonary metastasectomy
Predictors of outcome – 3 or fewer pulmonary mets, long disease free interval
Bilaterality of disease not significant

13. Billingsley et al, Cancer, 82(2): p. 389.
230 patients with metastatic STS
Predictors of outcome after multivariate analysis – complete resection of metastatic disease, disease free interval> 12 months, absence of preceeding LR, age < 50
Factors in long term survivors (> 36 months) – complete resection of metastatic disease, tumor size < 5cm

14. Zagars et al, Int J Rad Onc Biol Phys 57(3): p. 739.
402 patients with localized STS who developed recurrent or metastatic disease
Of those with metastatic disease, factors for survival included – complete resection of metastases, disease free interval > 1 year, absence of prior chemotherapy
Site of metastasis (lung vs. other) not a significant factor

15. Purpose
To investigate predictors of outcome of patients who present with primary AJCC stage IV soft tissue sarcoma who are treated with surgical resection of their primary tumor.

16. Methods
REB approval
Retrospective review of prospectively collected database at Mount Sinai Hospital from years 1986 – 2006
Inclusion – resection of primary tumor (either limb salvage or amputation)

17. Methods Survival analysis – Kaplan-Meier – log rank
Cox proportional hazards analysis for factors found to be significant on univariate analysis

18. Results 1537 patients 130 presented with AJCC stage IV (8.5%)
Mean age 56 years (range years)
75 male, 55 female
Median survival 11 months (range months)

19. Presenting Status Presentation # of patients (%) Lung mets only
81 (62)
Lymph node mets only
20 (10)
Lung & lymph node mets
13 (15)
Presentation as metastasis
16 (12)

22. Tumor Factors # of patients (%) Depth Superficial 14 (11) Deep
116 (89)
Size
< 5cm
21 (16)
> 5cm
109 (84)
Grade 1
5 (4) 2
20 (15) 3
105 (81)

23. Treatment Factors # of patients (%) Type of Surgery Limb Salvage
115 (88)
Amputation
15 (12)
Chemotherapy
Yes
48 (37) No
82 (63)
Radiation
78 (60)
52 (40)

25. Univariate Analysis for Overall Survival (log rank)
Factor
Significance (p-value)
Anatomic location
0.5
Depth
0.11
Gender
0.35
Histologic subtype
0.15
Bilateral vs. unilateral lung mets
0.62
Pulmonary metastasectomy
0.32
Use of chemo
0.53

26. p=0.0006

27. p=0.02

28. p=0.05

29. p=0.04

30. Cox model Factor Significance Hazard Ratio
# of lung mets (<=3 vs. >3)
0.09
0.6
Lymph node vs. lung mets
0.008
2.7
Grade
0.8
0.9
Size
0.15

31. Survival > 3 or >6 months
We dichotomized outcome into survival of < 3 months or > 3 months, or < 6 months or > 6 months
The same factors maintained prognostic significance
No other factors demonstrated significance
Therefore the same factors can be used to predict longer survival

32. Discussion Patients presenting with stage IV STS have dismal prognosis
Patients with lymph node mets rather than lung mets can occasionally be cured by aggressive surgical management

33. Discussion
Other factors including small primary tumor size, low grade and fewer than 4 pulmonary metastases may suggest more indolent course
These may also benefit from aggressive treatment to prolong survival

34. Is survival the best outcome in deciding on correct treatment?
Obviously not
Patients must be told from the outset that their prognosis is poor
However other outcome measures may be useful in evaluating effectiveness of what should be considered palliative surgery

35. Quality of life measures
Symptom specific
McGill Pain Index
Generic functional assessment
Karnofsky performance status
Secific quality of life assessments
Function assessment of cancer therapy (FACT)
Edmonton symptom assessment system

36. Future studies
Prospective evaluation of effectiveness of surgery in improving quality of life in patients undergoing palliative resection of STS
Development of disease-specific quality of life outcome measure for palliative sarcoma surgery

37. Conclusions
Patients presenting with metastatic soft tissue sarcoma with isolated lymph node metastases, fewer than 4 lung metastases, low grade tumours or tumours less then 5 cm have better survival on univariate analysis
Isolated lymph nodes mets only significant prognostic factor on multivariate analysis
Aggressive surgical treatment of the primary and metastasis with curative intent may be warranted in small group of patients