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Soft tissue sarcoma-What is the role of Radiation

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A short presentation on briefly about management outline and details of Radiation therapy in soft tissue sarcomas.

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Soft tissue sarcoma-What is the role of Radiation

  1. 1. MANAGEMENT OF SOFT TISSUE SARCOMA Dr Sanudev SadanandanV P Senior Registrar Dept of Radiation Oncology Baby Memorial Hospital
  2. 2. Contents  Introduction  Etiology & Presentation  Investigation,Staging,Pathological classification  Management -Surgery -Radiotherapy -Chemotherapy  Retroperitoneal sarcoma  Follow up  Prognostic factors  Summary
  3. 3. Introduction  mesenchymal neoplasms  Adult <1%  paediatric neoplasms 15%  Incidence in United states 11280 cases in 2012
  4. 4. Introduction  Can occur at any site Extrimities 43% Visceral 19% Retroperitoneal 15% Trunk/thoracic 10% Other 13%  Lower extremity > trunk > upper extremity > H&N .
  5. 5. Etiological factors  Genetic mutations-NF-1, RB, Gardner’s syndrome, LF syndrome  Radiation exposure (osteosarcoma, angiosarcoma)  Chronic lymphoedema- Angiosarcoma  Chemical exposure eg. arsenic, polyvinyl chloride (hepatic angiosarcoma)  Infections eg. HHV-8: Kaposi’s Sarcoma
  6. 6. WHO PATHOLOGICAL CLASSICATION 2002 Adipocytic tumors-Liposarcoma Chondro osseous tumor-CS/OS Fibroblasic/myofibroblastic tumor Undifferentiated tr Fibrohystiocytic tr-MFH 1.Synovial 2.Epitheloid 3.Alveolar soft part sa 4.Clear cell sarcoma 5.Extraskeletal myxoid chondrosarcoma 6.Extraskeletal Ewings/PNET 7.Desmoplastic small round cell tr 8.Extrarenal rhabdoid tr 9.Undifferentiated sarcoma/NOS Smooth muscle -Leiomyosarcoma Skeletal muscle-RMS Vascular-AS Periferal n-Malignan peripheral nerve sheath tr
  7. 7. EXTREMITY SOFT TISSUE SARCOMA
  8. 8. Presentation  Asymptomatic mass-MC  Pain - 33%  Paraneoplastic symptoms eg. Fever  Nodal swellings -Rare  Features of Metastasis –Cough, Dyspnoea, Hemoptysis (10%)
  9. 9. INVESTIGATION  ESSENTIAL Routine inv MRI Scan +/- CT Scan CT Chest True cut Biopsy/Incision Biopsy  OTHER USEFUL INV IN SELECTED SITUATIONS Abdominopelvic CT Scan-AS,LMS,ES,M/RC-LS MRI Total spine-M/RC LS MRI/CT Brain- AS,Alveolar softpart PET CT
  10. 10. STAGING
  11. 11. MANAGEMENT ONCO PATHOLOGIST IMAGEOLOGIST SURGICAL ONCOLOGIST ORTHOPEDICONCOLOGIST RADIATION ONCOLOGIST MEDICAL ONCOLOGIST MULTIDISCIPLINARY TEAM
  12. 12. STAGE WISE MANAGEMENT IA LG SX--FOLLOW UP IB LG SX ONLY if margin adequate SX –PORT if close/positive margin IIA Resectable without functional loss SX—PORT IIB,III Resectable without fuctional loss SX ---PORT
  13. 13. Synchronous Stage IV Single organ ,limited tumor bulk, amenable to complete resection Disseminated Primary tr mx +Metastatectomy/SBRT +/- CT +/-RT Palliation + BSC
  14. 14. SURGERY  First intervention  Most effective treatment to ensure cure.  Function preservation  Adequate Oncologic clearance
  15. 15. SURGERY BIOPSY -TRUCUT/OPEN -EXPERIENCEDSURGEON -NOVIOLATIONOF FASCIAL PLANES -NEEDLETRACK & SCARTO BE EXCISEDATTHETIMEOF DEFINITIVE SURGERY *WIDE EXCISION WITH NEGATIVE MARGINS *LIMB SALVAGE SURGERY Minimum margin 1 cm Close <1 cm margin AMPUTATION -GROSSTOTAL RESECTION IS EXPECTEDTO RENDER LIMB NON FUNCTIONAL -AT PATIENT PREFERENCE
  16. 16. PATHOLOGIC ASSESSMENT HISTOPATHOLOGY REPORT Organ/site/Sx Status of Margin Primary Diagnosis-WHO Depth of tumor Status of LN Size of tumor Other studies IHC/EM Molecular genetics Grade-NCI-Histo/Loc/Necrosis -FNCLCC-diff/mito count/necro Additional Mitotic rate Vascular invasion inflamatory infiltrate Necrosis +/-,Type,% TNM Stage.
  17. 17. RADIOTHERAPY
  18. 18. INDICATIONS-PORT 1.All deep seated tumors 2.All high grade tumors ,size>5cm 3.Intermediate grade tumor size >5cm 4.Repeated margin positivity 5.Tumor >5cm superficial 6.Close margin Intermediate/High grade
  19. 19. INDICATIONS-PREOP RT  Unresectable disease  Resectable disease but resection will lead to significant functional loss
  20. 20. PREOP RT PORT Treatment volume smaller-No need to cover operated field Treatment volume larger Reduce seeding during surgery More seeding Tumor regression and better resectability Decreased risk of recurrence Less toxic More toxic No hypoxia-Blood supply uninterrupted Hypoxia in tumor bed may adversely affect oucome Disadv-Poor wound healing -No complete HPR Adv-Complete HPR available
  21. 21. RADIOTHERAPY PLANNING  Positioning & Immobilisation  Planning CT Scan 3-5 mm cuts with iv contrast  Co register Preoperative MRI /CT  3DCRT/IMRT preferred
  22. 22. RADIOTHERAPY PLANNING  GTV –contour tumor in preop MRI –T1C  CTV ---Initial GTV + Margin to encompass microscopic spread ---Surgical Scar/Drain sites/Surgical clips ---GTV to CTV Margin 3 cm longitudinally (RTOG) 1.5 cm laterally
  23. 23. CTV-PTV Margin 5-10 mm  OAR & Constraints—Depends on primary site.
  24. 24. Example Case  55-year-old male with a large high-grade round cell liposarcoma in right distal thigh. Clinical stage (AJCC 7th edition) IIIT2bN0M0G3.  The MRI of right distal thigh showed a large well circumscribed heterogeneous, multiloculated mass located within the posterior thigh.   The tumor measured 14.8 cm in craniocaudal dimension, 7.8 cm in AP dimension, and 11.3 cm in maximal medial-lateral dimension.  Simulation CT images were fused with those from the diagnostic thigh MRI
  25. 25. ←CTV
  26. 26. ←CTV
  27. 27. ←CTV
  28. 28. ←CTV
  29. 29. ←CTV
  30. 30. ←CTV
  31. 31. ←CTV
  32. 32. ←CTV
  33. 33. ←CTV
  34. 34. ←CTV
  35. 35. ←CTV
  36. 36. ←CTV
  37. 37. ←CTV
  38. 38. ←CTV
  39. 39. ←CTV
  40. 40. GTV→ ←CTV
  41. 41. GTV→ ←CTV
  42. 42. GTV→ ←CTV
  43. 43. GTV→ ←CTV
  44. 44. GTV→ ←CTV
  45. 45. GTV→ ←CTV
  46. 46. GTV→ ←CTV
  47. 47. GTV→ ←CTV
  48. 48. GTV→ ←CTV
  49. 49. GTV→ ←CTV
  50. 50. GTV→ ←CTV
  51. 51. GTV→ ←CTV
  52. 52. GTV→ ←CTV
  53. 53. GTV→ ←CTV
  54. 54. GTV→ ←CTV
  55. 55. GTV→ ←CTV
  56. 56. GTV→ ←CTV
  57. 57. GTV→ ←CTV
  58. 58. GTV→ ←CTV
  59. 59. GTV→ ←CTV
  60. 60. GTV→ ←CTV
  61. 61. GTV→ ←CTV
  62. 62. GTV→ ←CTV
  63. 63. GTV→ ←CTV
  64. 64. GTV→ ←CTV
  65. 65. GTV→ ←CTV
  66. 66. GTV→ ←CTV
  67. 67. GTV→ ←CTV
  68. 68. GTV→ ←CTV
  69. 69. GTV→ ←CTV
  70. 70. GTV→ ←CTV
  71. 71. GTV→ ←CTV
  72. 72. GTV→ ←CTV
  73. 73. GTV→ ←CTV
  74. 74. GTV→ ←CTV
  75. 75. GTV→ ←CTV
  76. 76. GTV→ ←CTV
  77. 77. GTV→ ←CTV
  78. 78. GTV→ ←CTV
  79. 79. GTV→ ←CTV
  80. 80. GTV→ ←CTV
  81. 81. GTV→ ←CTV
  82. 82. GTV→ ←CTV
  83. 83. GTV→ ←CTV
  84. 84. GTV→ ←CTV
  85. 85. GTV→ ←CTV
  86. 86. GTV→ ←CTV
  87. 87. GTV→ ←CTV
  88. 88. GTV→ ←CTV
  89. 89. GTV→ ←CTV
  90. 90. GTV→ ←CTV
  91. 91. GTV→ ←CTV
  92. 92. GTV→ ←CTV
  93. 93. GTV→ ←CTV
  94. 94. GTV→ ←CTV
  95. 95. GTV→ ←CTV
  96. 96. GTV→ ←CTV
  97. 97. GTV→ ←CTV
  98. 98. GTV→ ←CTV
  99. 99. GTV→ ←CTV
  100. 100. GTV→ ←CTV
  101. 101. GTV→ ←CTV
  102. 102. ←CTV
  103. 103. ←CTV
  104. 104. ←CTV
  105. 105. ←CTV
  106. 106. ←CTV
  107. 107. ←CTV
  108. 108. ←CTV
  109. 109. ←CTV
  110. 110. ←CTV
  111. 111. ←CTV
  112. 112. ←CTV
  113. 113. Brachytherapy  Surgical resection + Frozen section  Place tumor bed clips  HDR tube placed at 1cm spacing  Target vol –Tumor + 2cm margin  Planning-Paris system  Load on POD4/D5
  114. 114. IORT  Surgical resection + Frozen section  TV=Tumor with 2 cm margin  Electrons/photons  Single sitting
  115. 115. DOSE-PORT
  116. 116. PREOP RT
  117. 117. Trials Trial Results Pisters et al 160 extremity & trunk Randomized to BT/Obs 42–45 Gy over 4–6d) BT-LC for high-grade lesions (65–90%), but not for LG. No difference in DSS /DM. NCI (Yang et al. 1998): rct 140 ,extremity sarcoma, WLE. LG to obs vs. PORT HG post-opCT vs. post-op chemo-RT. RT = large field to 45 Gy → boost to 63 Gy. RT increased LC for low-grade (60% vs. 95%) and high-grade (75% vs. 100%). No difference in OS /DMFS NCI (Rosenberg et al. 1982): 43 , HG STS ,extremity WLE + PORT vs. amputation alone. RT = 45–50 Gy to compartment with boost to 60–70 Gy. No difference in LC, OS, or DFS. Chemo decreased LR and increased DFS (60% vs. 90%) and OS (75% vs. 95%).
  118. 118. Pre-op or Post-op RT NCIC (O’Sullivan et al. 2002; Davis et al. 2005): 190 patients with extremity STS randomized pre-op RT (50 Gy) vs. post-op RT (66 Gy). If +margins, pre-op got 16 Gy boost.. No difference LC /DM /PFS Preop-woundhealing PORT-late fibrosis Pollack et al. (1998): post-op RT (60–66 Gy) Vs pre-op RT (50 Gy) before excision or reexcision. . No difference in LC presenting with gross disease, best LC with pre- op RT (88% vs. 67%) presenting after excision - immediate reexcision and post-op RT (LC 91% vs. 72%). wound-healing --pre-op
  119. 119. IORT Oertel et al. (2006): n=153 primary or recurrent extremity STS limb-sparing surgery + IORT 10–20 Gy → post-op EBRT 36–50 Gy. Five-year OS 77%, DMFS 48%, and LC 78%. IORT dose >15 Gy improved LC, but EBRT <45 or 45 Gy not significant for LC. Acute wound-healing toxicity.-High NCI (Sindelar et al. 1993): N=35 ,resectable retroperitoneal STS randomized to surgery + IORT 20 Gy → post-op 35–40 Gy vs. surgery → post-op 50– 55 Gy. No difference in 5-year OS (35%), nonsignificant increase in LC ,IORT increased neuropathy if >15 Gy. Alektiar et al. (2000): primary or recurrent retroperitoneal STS surgery + IORT 12–15 Gy → post-op EBRT 45–50 Gy. 5-year OS 55%, DMFS 80%, LC 62%, 10% neuropathy
  120. 120. BENEFIT OF PORT  Enucleation-80% recurrence  WE with negative margin- 30%  WE with negative margin and PORT-5%  Adjuvant radiotherapy improves local control without benefit in Overall survival
  121. 121. Toxicities  Hair loss  Skin telangictasia  Skin fibrosis  Lymphoedema  ORN  Pathological #  Radiation induced 2nd malignancies
  122. 122. CHEMOTHERAPY  Indications 1. Adjuvant HG extrimity sarcoma Tumor size >5 cm 2.Neoadjuvant Unresectable disease 3.Palliative To palliate symptomatic mets
  123. 123.  Regimen ADR 60mg/m2 IV D1 IFOSFAMIDE 1.3gm/m2 IV D1-D3 q3weekly x 6 cycle  2nd line Doce+Gem,Pazopanib
  124. 124. Benefit in adjuvant setting  Metaanalysis ( Pervaiz et al. 2008):  N=1,953 resectable STS  WLE ± RT ---observation vs. adjuvant doxorubicin-based chemo.  Chemo improved LC (absolute 4%), DMFS (9%), RFS (10%), and OS (6%).  Specifically doxorubicin/ifosfamide improved LC (absolute 5%, not significant), DMFS (10%), RFS (12%), and OS (11%).  No trial of pre-op vs. post-op chemo.
  125. 125. MANAGEMENT OF RETROPERITONEAL SARCOMA
  126. 126.  34% of all STS  MC- liposarcoma (40%), leiomyosarcoma (25%), malignant peripheral nerve sheath tumour and fibrosarcoma  MC visceral STS -GIST, leiomyosarcoma and desmoid tumour
  127. 127. Presentation  Asymptomatic mass  Pain  Gastrointestinal bleeding  Incomplete obstruction  Neurological symptoms due to invasion of neurovascular structures
  128. 128. Imaging  CT-abdomen  Also allows evaluation of the liver, the most common site of metastasis  Staging  No official staging system  The same grading system applies as for extremity STS
  129. 129. Diagnosis  Laparotomy with open biopsy  CT guided biopsy has a limited role only  Only if: - unresectable tumour - doubtful diagnosis - neoadjuvent chemotherapy considered
  130. 130. Treatment  Surgery -The mainstay of treatment  Chemotherapy principles are the same as for extremity STS  Radiotherapy -High morbidity and mortality due to radiosensitivity of surrounding organs -Intensity-modulated radiation showing promising results
  131. 131. prognosis  Adverse factors for local recurrence: + margins >50 years age deep location fibrosarcoma type including desmoid, malignant peripheral nerve sheath tumors.  Adverse factors for distant metastasis: high-grade (at 5 years, <10% for low-grade, 50% for high grade) increasing size deep location, leiomyosarcoma or malignant peripheral nerve sheath tumor high Ki-67.
  132. 132. Follow up  H&P  CXR/CT Chest 3-6 mon x 2-3 yr 6monthly x 2yr Annual  Baseline and periodic imaging of primary site
  133. 133. Recurrence  Local relaspse-Work up  Metastasis Single organ &Limited tumor bulk- Metastatectomy+/-CT/RT Ablation Isolated Node-Nodal dissection+/- RT/CT Disseminated mets-Palliation
  134. 134. Survival StageI extrimity 5-year LC 90–100%, OS 90% II–III extremity ~5-year LC 90%, OS 80% for stage II, 60% for stage III. For recurrence, amputation salvages ~75% Stage IV EXTRIMITY Limited mets~5-year OS ~25%. Disseminated ~5-year OS 10% Retroperitoneal ~5-year LC 50%, DM 20–30%, OS 50%
  135. 135. Take home message  STS are hterogeneous neoplasms  Management of STS requires multidisciplinary tumor boards and close collaboration between specialists.  Surgery is the most important form of treatment  Radiotherapy helps to improve local control.  Chemotherapy can be utilised in selected situations in adjuvant/Neoadjuvant treatment.
  136. 136. References  NCCN V2.2014  Textbook of Radiotherapy planning –Dobbs  Textbook of Radiation Oncology-Leibel Philips,Perez  RTOG Sarcoma contouring guideline  Online resources
  137. 137. THANKYOU
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A short presentation on briefly about management outline and details of Radiation therapy in soft tissue sarcomas.

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