Soft tissue sarcomas are a heterogeneous group of malignancies that present significant challenges for diagnosis and management. Multidisciplinary care is essential but multidisciplinary teams need expertise in sarcoma pathology and non-extremity sarcomas. There is uncertainty around the optimal use of chemotherapy, its sequencing with radiation, and its role for retroperitoneal sarcomas. Surveillance imaging requires further study to identify the most cost-effective strategies.

1. Practical considerations in
soft tissue sarcoma
Dr Sameer Rastogi
Assistant Professor
Sarcoma Medical Oncology
Dr BRA IRCH, AIIMS
Samdoc_mamc@yahoo.com

2. Soft tissue sarcomas
• 1% of all adult malignancies.
• More than 50 histological subtypes-HETEROGENOUS and COMPLEX
• Ubiquitous in their site of origin
-Extremity (43%), Trunk(10%), Visceral(19%), RP(15%)

3. Taylor et al. Nature reviews. 2011

4. CHALLENGES
• Multidisciplinary care
• Diagnosis
-Pathology
-Molecular testing
• Histology specific imaging
• Management
- When to give chemotherapy? -Which chemotherapy?
- sequence - Adjuvant v/s NACT
- ? RT first/chemo first
-Histology tailored chemotherapy
• Retroperitoneal sarcoma

5. Multidisciplinary care
• Mandatory in all cases
• Pathologists, radiologists, surgeons, radiation oncologist, medical
oncologists and paediatric oncologists, nuclear medicine specialists,
organ-based specialist, plastic surgeon
• NCCN-- patients with sarcoma should be managed, but not
necessarily treated, by a multidisciplinary panel who have heavy
experience

7. Benefits

8. CHALLENGES
• Multidisciplinary care
• Diagnosis
-Pathology
-Molecular testing
• Staging
• Management
- When to give chemotherapy? -Which chemotherapy?
- sequence - Adjuvant v/s NACT
- ? RT first/chemo first
-Histology tailored chemotherapy
• Retroperitoneal sarcoma

10. ● Compared sarcoma unit’s histopathology reports with
referring reports on 349 specimens
● Diagnostic agreement was found only 256/ 349 cases
(73.4%)
● Further supported NICE guidelines that all cases of sarcoma
should be reviewed by bone and soft tissue specific
pathologist
Thway et al. Sarcoma. Volume 2009 (2009), Article
ID 741975

12. Discordance of histo-pathological diagnosis
of patients with soft tissue sarcoma
referred to tertiary care center.
● January 2016 to January 2017
● Retrospective analysis – referred to sarcoma medical
oncology clinic (AIIMS) (Both intra institutional and from
other institutes)
● Major discrepancy and Minor discrepancy
Sameer Rastogi, Aditi Aggarwal, Kamal Raj Soti, Ilavarasi Vanidassane, Mehar C Sharma, Ajay Yadav,
Aparna Sharma, Babita Kataria, and S. V. S. Deo JCO 2017 35:15_suppl, 11064-11064

13. Patient characteristics
● N =142
● Median Age 40 years.
● M- F 65:35
● Non metastatic / metastatic 58% / 42%
● N=97 with outside diagnosis
● 15% had FNAC report
Sameer Rastogi, Aditi Aggarwal, Kamal Raj Soti, Ilavarasi Vanidassane, Mehar C Sharma, Ajay Yadav,
Aparna Sharma, Babita Kataria, and S. V. S. Deo JCO 2017 35:15_suppl, 11064-11064

14. Characteristics (n=149) Number (%)
Site
Extremity
Non extremity
Retroperitoneal
Head and neck
Trunk
Others
52 (35)
97 (65)
23 (15)
22 ( 15)
20 (13)
22 (22)
Histopathology subtype
Synovial sarcoma
MPNST
Liposarcoma
Soft tissue ewings sarcoma
Leiomyosarcoma
Pleomorphic undifferenttiated sarcoma
Others
25 (17)
13 (9)
13 (9)
13 (9)
12 (8)
12 (8)
61 (40)

15. Discordance in histopathology (n=97)
percentages
major discrepancy
minor discrepancy
no discrepancy
37%
39%
24%
Sameer Rastogi, Aditi Aggarwal, Kamal Raj Soti, Ilavarasi Vanidassane, Mehar C Sharma, Ajay Yadav,
Aparna Sharma, Babita Kataria, and S. V. S. Deo JCO 2017 35:15_suppl, 11064-11064

16. Multivariate analysis for major discrepancy
Type of outside hospital
Private
Public
35.7%
40%
0.867
Location of tumor
Extremity
Non extremity
19.4%
48%
0.005
Type of sample outside
Biopsy
FNAC
34.5%
53.8%
0.18
Age at presentation
Less than or =40 years
More than 40 years
41%
31% 0.32

18. Critical Analysis
● STS pathology is intricate and we need to collaborate and
develop sarcoma pathology expertise
● FNA Should not be done
● Specific focus on non extremity sarcoma

21. CHALLENGES
● Multidisciplinary care
● Diagnosis
-Pathology
-Molecular testing
● Imaging
● Management
- When to give chemotherapy? -Which chemotherapy?
- sequence - Adjuvant v/s NACT
- ? RT first/chemo first
-Histology tailored chemotherapy
● Retroperitoneal sarcoma

22. IMAGING
● Chest spiral CT scan is mandatory
● Regional assessment-clear cell sarcoma and epitheloid sarcoma
● Abdominal CT- Limb myxoid liposarcoma
● Brain CT- alveolar soft part sarcoma, clear cell sarcoma and
angiosarcoma NCCN 2017, UK Taskforce guidelines 2016

25. PET CT
● No proven role yet in routine management of Soft tissue
sarcoma
● Might have some role in seeing disease sites before
adjuvant surgery
● Utility in NF associated MPNST? For the lesion selection
and behaviour (to differentiate plexiform NF vs MPNST)

29. CHALLENGES
● Multidisciplinary care
● Diagnosis
-Pathology
-Molecular testing
● Imaging
● Management
- When to give chemotherapy? -Which chemotherapy?
- sequence -- - ? RT first/chemo first
- Adjuvant v/s NACT
-Histology tailored chemotherapy
● Retroperitoneal sarcoma

30. ROLE OF CHEMOTHERAPY
● TIMING
NACT v/s ADJUVANT- WHICH REGIMEN ?
- NUMBER OF CYCLES?
● Timing of chemotherapy
● After completion of RT?
● Before RT begins ?

31. Adjuvant therapy- old

32. ● Number of trials = 14
● Number of patients = 1548
● ONLY INDIVIDUAL PATIENT DATA TILL DATE
Lancet 1997; 350: 1647–54

33. The absolute benefit deriving from chemotherapy was 13% at 2 years and
increased to 19% at 4 years (P = .04). Hence this trial was stopped
Meta analysis – trials --- Meta analysis – Trials --- Meta analysis – Goes on

34. Cancer 2008

35. Lancet 2012
Surgery was follwed by Chemotherapy follwed by RT vs Sx followed by RT

36. Again meta analysis done, reported with this trial which
showed maintained survival benefit

37. Metaanalysis
Trial

38. CHALLENGES
● Multidisciplinary care
● Diagnosis
-Pathology
-Molecular testing
● Imaging
● Management
- When to give chemotherapy? -Which chemotherapy?
- sequence -- - ? RT first/chemo first
- Adjuvant v/s NACT
-Histology tailored chemotherapy
● Retroperitoneal sarcoma

40. Local failure in both arms in EORTC 62931 was
Chemotherapy  RT vs Sx RT (17% vs 23%)

41. CHALLENGES
● Multidisciplinary care
● Diagnosis
-Pathology
-Molecular testing
● Imaging
● Management
- When to give chemotherapy? -Which chemotherapy?
- sequence -- - ? RT first/chemo first
- Adjuvant v/s NACT
-Histology tailored chemotherapy
● Retroperitoneal sarcoma

44. RPS – SPECIAL ENTITY
● Biological behaviour different
● 80% recurrences-local
● <10% -lung
● ?Role of chemo-? Detrimental
?NACT v/s Adjuvant- no prospective
randomised data
● ?Role of RT-

45. worse median OS among the CT cohort -40 vs 52 months, p = 0.002

46. Gronchi et al. J Clin Oncol 31:1649-1655
Grade 1- Grade 1 Grade 1
60
Grade 2 120
Grade 3 160

47. Follow up

48. Why value still remains unproven?
● No randomized trial and benefit based upon single institution
registries and single institution series with no definition of
denominator.
● Many UK institution select patients based upon certain
criteria
● Less than 10 metastasis
● Absence of new lesions in last 3 months1
1.Communication with Dr Ian Judson (Royal Marsden, London)

50. Abstr #11069 Clinical utility of surveillance…. Lim et al, Singapore

51. • Cost effective analysis for competing imaging modalities performed
at NCCN/ ESMO guideline specified intervals
• Markov’s model was used for simulating lifetime outcomes for
patients with stage II-III soft tissue sarcoma in NED state
and followed up with various modalities.
Abstract 11021 Asco 2017

52. Methods used

53. Incremental Cost-effectiveness Ratio (ICER)<br />

54. Incremental Cost-effectiveness Ratio (ICER)<br />

55. Incremental Cost-effectiveness Ratio (ICER)<br />

56. Incremental cost-effectiveness ratios (ICERs) for each distant recurrence surveillance strategy

57. Critical Comment

58. Take home message
● Multidisciplinary meeting – most important
● Pathology
● Imaging
● Chemo yes no, after or before RT
● Follow up