The Evolution of Pediatric Extremity Tumor Surgery

This Grand Rounds presentation by Dr. Daniel Li at The Ohio State University, focuses on a pediatric oncology case involving the extremity. The patient was treated by Dr. Scharschmidt, the head of pediatric oncology at Nationwide Children's Hospital. The presentation will explore the evolution of treatment approaches over time, evaluate various treatment modalities, and provide a detailed overview of the surgical team's interventions. Additionally, a comprehensive literature review will be integrated throughout the discussion."

The title of this presentation is a play on Stanley Kubrick's 1964 black comedy as it explores the absurdities of nuclear conflict and Cold War tensions between the United States and the Soviet Union. Dr. Strangelove, a bizarre former Nazi scientist is now advising the U.S. president on nuclear strategy.

The subtitle "How I Learned to Stop Worrying and Love the Bomb" an ironic embrace of the atomic era, delving into the unintended consequences of nuclear deterrence strategies. This phrase encapsulates the film's exploration of the paradoxical acceptance of immense power and the complex ramifications that follow. The subtitle of this presentation, "how I learned to stop worrying embracing the metal” is somewhat of a tongue-in-cheek comment with respect to innovation in orthopedics as they come with their own set of unforeseen outcomes, posing new challenges and complications that need to be managed. There is a parallel need to embrace change, new technologies, and surgical techniques with rational optimism.

1. Dr. Scalpelove or: How I Learned to Stop Worrying and Embrace the Metal The Evolution of Pediatric Extremity Tumor Surgery

2. Daniel Li, MD The Ohio State University Thomas Scharschmidt , MD, Professor Director of Pediatric Oncology at Nationwide Children’s Hospital

3. Case Presentation

4. 6M p/w Intermittent Limp and L Knee Pain for 2 Weeks

5. 6M w/ L knee pain c/f malignancy CT Chest negative PET scan with focal uptake Other W/U ( ie EKG/echo) negative Bx : osteosarcoma

6. 6M w/ L knee pain c/f malignancy CT Chest negative PET scan with focal uptake Other W/U ( ie EKG/echo) negative Bx : osteosarcoma Treatment?

7. Background and Historical Context

8. ‘Turn-up’ Plasty

9. ‘Turn-up’ Plasty

10. JBJS 1972

11. Historical Context Pre-1970s: amputation for high-grade sarcoma 5-year survival rate <20% CT/MRI developed in 1970-1980s 1970s: advances in chemo 5-year survival rate 55-70%

12. Optimal surgical treatment in children? Limb-salvage preserves more function Achievable up to 90% of cases Remaining growth and size of bone present substantial hurdles Located close to the physis (75% of cases) Repeated invasive procedures Technologic advances/longevity of prosthesis

13. Biologic Reconstruction

14. Intercalary Grafts

15. Intercalary Osteosynthesis 1 Year

16. Autograft-Allograft Composite Open Physis

17. Transepiphyseal Osteotomy

18. 16M w/ Osteosarcoma Abutting Physis

19. 5-Year Post-Op

20. Used independently or to augment allo / autograft Potential physeal longitudinal growth and remodeling Revision grafting for failed osteosynthesis 6F Ewing’s sarcoma s/p primary recon with free fibula flap Vascularized Fibular Flaps

21. 6M w/ Ewing’s sarcoma of L proximal femur Fractured initial allograft reconstruction Underwent revision with free fibula flap LEFT (1 mo. post-op): evidence of prior allograft fracture RIGHT (5 years post-op): hypertrophy to native femur size Vascularized Fibular Flaps

22. Intercalary defects are reliably treated with limb salvage Long-term success rates and good functional outcomes in > 80% of patients Biologic reconstruction; potentially physeal sparing High rates of infection (20%), fracture (30%), and delayed/non-union (50%)

23. Osteoarticular Allografts

24. Osteoarticular Allografts For tumors that involve the physis Requires matching of articular congruity 10-year allograft survival rates up to 70% Questionable chondrocyte viability Early joint degeneration Biologic spacers/bone stock for TJA

25. 75 total allografts (1962-1997) 13 (17%) died 2/2 tumor without graft failure Minimum F/U 10 years At 10 years… Allograft survival: 78% Joint survival (no conversion to TKA): 71% Limb preservation: 97%

26. Caudal Cranial

27. Post-Op (Immediate, 5 Years, 10 Years) Preserved Joint Space

28. Distraction Osteogenesis and Bone Transport

29. Femoral Shortening Distraction

30. Femoral Shortening Distraction

31. Femoral Shortening Distraction

32. Femoral Shortening Distraction

33. Fixator-Assisted Tibial Bone Transport

34. Fixator-Assisted Tibial Bone Transport

35. Fixator-Assisted Tibial Bone Transport 9 Years

36. Endoprosthesis

37. Limb Salvage

38. Early Experiences Austin Moore Vitallium (CoCr), 1943 Palliative treatment for those that refused amputation Surgery delayed until prosthesis could be fabricated Development of preoperative chemotherapy

39. Custom Prosthesis ( Howmedica , 1980s)

40. HMRS 1988 GMRS 2002 Development of Modularity KMFTR 1986

41. We’ve Come a Long Way…

42. Considerations in growing children: Fixation: immediate stability and weight-bearing Cement vs. Press-fit: limited cement mantle in small children Delayed osseous ingrowth during chemotherapy? Long-term osseointegration: bone stock and quality Capacity for extension: Avoids multiple surgical procedures and general anesthesia Lower morbidity, cost savings, less psychological trauma

43. Expandable Endoprosthesis

44. Sequential Lengthenings

45. Lewis Expandable Adjustable Prosthesis (LEAP)

46. Lewis Expandable Adjustable Prosthesis (LEAP)

47. Stanmore II (Ball-bearings, 1982)

48. Stanmore II (Ball-bearings, 1982)

49. Stanmore III (C-collars, 1988)

50. Stanmore III (C-collars, 1988)

51. Stanmore IV MIS (Jack-screw, 1993)

52. First Non-Invasive Expansion Device (1990s, France)

53. Mechanism: “spring in a tube” Spring is compressed in a polymer matrix EM induction heats polymer Less viscosity allows spring to expand Spring’s potential energy is converted Expansion stops once polymer cools Phenix ( Repiphysis ) Expandable Prosthesis

54. Repiphysis Failure Single institution, 10 patients Minimum 5-year follow-up Severe pain with lengthening Required general anesthesia Exact expansion of implant unpredictable and difficult to control 9/10 Required revision surgery 8 Mechanical failures

55. Stanmore Non-Invasive Extendable Prosthesis (2003)

56. Stanmore Non-Invasive Extendable Prosthesis (2003)

57. Largest reported Stanmore-design series (2002-2009) 44 patients (avg. 11.4 years old) with mean F/U 3.4 years 10 (18%) died due to disseminated disease Average lengthening of 4 cm Mean MSTS score 24.7/30; no local reoccurrence of tumour Complications in 16 patients (30%) 10 patients required revision (18%)

58. Case Resolution

59. 6M L Knee Osteosarcoma

60. Custom Stanmore Prosthesis

61. Custom Stanmore Prosthesis

62. 2-Years Post-op

63. Long-term outcomes TBD…

64. Physeal Arrest

65. 124 Patients from 1982-2008 at the Royal Orthopaedic Hospital, UK Minimum 10-year follow-up (average 24 years) Limb salvage achieved in 113 patients (91%) 10-year amputation-free rate of 93% Mean LLD at final follow-up: 1 cm 86% of patients reached target limb length Mean MSTS score 82% 10-year endoprosthetic failure-free survival rate of 28%

66. 90% of patients with complications 105 patients underwent 334 additional operations Average of 2.7 additional procedures per patient Excludes planned lengthenings

67. Complications…

68. Complications… On complications…

69. Complications… On complications… On complications…

70. 9M Osteosarcoma reconstruction with failure of the expansion mechanism 2 years post-op Mechanical Failure with Revision

71. Septic Loosening Requiring 2-Stage Revision

72. Septic Loosening Requiring 2-Stage Revision

73. Septic Loosening Requiring 2-Stage Revision

74. Enhancing Osteointegration

75. Enhancing Osteointegration

76. Thank you! Special thanks to Dr. Scharschmidt and Dr. Quinion

77. On-going Developments

78. “ BioXpand ” Growing Prosthesis Combines distraction osteogenesis with endoprothesis Increases the host-bone segment, not implant length Three Stages: 1. Dummy stem initially implanted 2. Replace stem with motorized lengthening nail ( Fitbone ) 3. Revise BioXpand components to conventional components

79. Compress Mechanism Anchor plug placed opposite spindle apparatus Spindle preloaded with compressed washers Acts as a longitudinal spring ‘Pushing against a fixed point’ Applies compressive forces of 400-800 lbs Hypertrophy and osseointegration at the bone-prosthesis interface

80. Combining Distraction Osteogenesis with Endoprothesis

81. “Sixty articles met the inclusion criteria; all were Level-IV evidence , primarily consisting of small, retrospective case series… The current state of the literature is limited and is complicated by under-segregation of the data by age and anatomical location of the reconstruction. ”

82. Literature with Encouraging Results…

83. Ewing’s Sarcoma Malignant small round blue cell sarcoma t(11:22) translocation (EWS-FLI1 fusion protein) +CD99 5-25 years old; pain, swelling, fevers Elevated ESR, WBC, LDH ~25% with macro- mets on presentation (lungs, bone) 10 year survival: 60% for localized disease 30% for metastatic disease Treatment: chemo + limb salvage (+/- adjuvant radiation)

84. Failure-free survival rate for patients surviving at-least 10 years… 57% at 5 years 28% at 10 years

85. Septic Loosening Requiring 2-Stage Revision

86. Mechanical Failure with Total Femur Replacement Revision

87. 112 patients (90%) experienced a total of 243 complications: Soft tissue related (27%) Stiffness/ arthrofibrosis Patellar maltracking Infection (10-20%) Both early (<2 years) and late (>2 years) Required 2-stage revision

88. 82 patients from 1998-2008 mean F/U 3.5 years 85% Survivorship at 5 years and 80% at 10 years “We conclude this is the most durable FDA-approved fixation method for distal femoral megaprostheses ”

89. Physeal distraction prior to tumor resection Preserves joint while allowing safe margin of excision 20 patients: avg. f/u of 4.5 years with 85% survival rate No patients with local reoccurrence Indications: - The tumour should be situated in the metaphyseal region - The physeal cartilage should be open - The tumour should not transgress the physis

90. Technical Considerations adequate resection margins restoration of limb length and normal axis of motion proper selection of components intra-operative adjustment, the torsional position between modules and the total length of the construct.

91. Operative Technique: 1. Ex-fix applied with 2 pins in the epiphysis and diaphysis ~10 cm beyond the tumor Distraction until ~2 cm of lengthening achieved 2. En -block wide resection of the tumor, sent for histologic examination 3. Reconstruction of the bony defect after confirmation of negative margins

92. Revision osteosynthesis (left to right): Immediate post-op images Non-union 8-months post-op Cancellous bone-grafting Persistent non-union Lateral strut graft with vasc -fib

93. Physeal Distraction

94. 14M w/ parosteal osteosarcoma: tibial allograft incorporation at 8 years Physeal Distraction

95. 22 patients who underwent bone distraction where epiphysis could be preserved Alternative to grafting: overcomes issues with revascularization/incorporation Improved biologic affinity, resistance to infection, and mechanical properties Mean distraction of 8 cm w/ average MSTS score of 91.5% (avg. 17 years)

96. Transepiphyseal Resection For tumors that abut but do not cross the physis Maintains native articular surface and soft tissue constraints Technically demanding and risks contaminating tissue planes Still requires sacrifice of the physis to achieve adequate margins

97. 13 patients at Italian Hospital of Buenos Aires from 1991-2000 Transepiphyseal resection of the proximal tibia or distal femur Indications: at least 1 cm of remaining epiphysis for fixation No patients with recurrence in the preserved physis At final follow-up (5 years), 11/13 patients with preserved epiphysis Average MSTS score of 27/30

98. 32 patients (avg. age 9) treated in Italy Stanmore, Repiphysis , and Kotz GMRS Overall survival: ~85% at 6 years Implant survival:~65% at 6 years Significantly higher for Kotz Implant Mean MSTS score 80%

99. 10F s/p osteosarcoma resection 1 month, 1 year, and 5 years post-op Total gain of 5 cm over 4 lengthenings However…

100. Osteosarcoma Malignant osteogenic tumor in children Pain, fever, swelling, mass DDx : Ewing’s Sarcoma Most commonly in distal femur and proximal tibia 20% of patients w/ pulm mets Bx : significant atypia and lacey osteoid Elevated ALP, LDH Treatment?