Malignant Bone Lesions

By admin On Apr 9, 2023

Ovid: Oncology and Basic Science

Editors: Tornetta, Paul; Einhorn, Thomas A.; Damron, Timothy A.

Title: Oncology and Basic Science, 7th Edition

> Table of Contents > Section I
– Evaluation and Management of Musculoskeletal Oncology Problems > 4
– Treatment Principles > 4.3 – Malignant Bone Lesions

4.3

Malignant Bone Lesions

Francis R. Patterson

Timothy A. Damron

Carol D. Morris

Malignancies involving bone include metastatic disease,
myeloma, lymphoma, and bone sarcoma. Treatment options include surgery,
radiotherapy, and chemotherapy. This chapter will focus on the
treatment principles involved in choosing the appropriate surgical
treatment along with appropriate adjuvant radiotherapy and/or
chemotherapy according to the diagnosis.

Surgical Treatment

Surgical Indications/Contraindications

Indications for surgical intervention of bone malignancies vary according to the underlying disease process (Table 4.3-1).

Biopsy for diagnosis
- Indications: plays a role in diagnosing
  nearly all bone malignancies, although multiple myeloma may often be
  diagnosed by serum or urine protein electrophoresis (SPEP or UPEP).
Prophylactic stabilization
- Indications: Impending pathologic
  fractures merit prophylactic fixation in many cases of metastatic
  disease, myeloma, and lymphoma.
- Contraindications: Except in unusual
  circumstances, bone sarcomas should be treated by wide excision, as
  instrumentation will potentially disseminate tumor locally and possibly
  systemically.
Open reduction and internal fixation (ORIF) pathologic fractures
- Same as for prophylactic stabilization
Extended intralesional curettage with adjuncts
- Indication: low-grade chondrosarcomas without soft tissue extension (as an alternative to wide resection)
- Contraindication: more
  aggressive-appearing chondrosarcomas (soft tissue extension and/or
  intermediate or high grade), all other bone sarcomas
Resection for extensive destruction
- Indications: Extensive symptomatic bony
  destruction that is not amenable to stabilization may warrant resection
  and reconstruction in the setting of metastatic disease, myeloma, and
  lymphoma.
  - Especially proximal femur and proximal humerus
  - Endoprosthetic reconstructions favored
  - Appropriate surgical margins range from intralesional to marginal or wide in this situation, as resection is not for cure.
- Contraindications: When internal fixation will suffice in metastatic disease, myeloma, and lymphoma, ORIF is preferred.
Resection for cure
- Indications
  - Solitary bone metastases (Box 4.3-1)
  - Most bone sarcomas (except intraosseous low-grade chondrosarcomas)

Resection of major segments of bone should not be
undertaken without considering (1) whether limb-sparing surgery or
amputation should be done, (2) whether reconstruction will be needed
for the defect left after limb-sparing surgery, and (3) what
reconstructive options should be considered.

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Table 4.3-1 Roles for Surgical Treatment According to Disease Process

Disease	Roles for Surgical Treatment	Appropriate Surgical Margin
Metastatic disease	Biopsy for diagnosis Prophylactic stabilization ORIF pathologic fractures Resection for extensive destruction Resection for cure (e.g., isolated renal carcinoma metastasis)	Intralesional Intralesional Intralesional Marginal or wide Wide
Multiple myeloma	Biopsy for diagnosis Prophylactic stabilization ORIF pathologic fractures Resection for extensive destruction	Intralesional Intralesional Intralesional Marginal
Lymphoma	Biopsy for diagnosis Prophylactic stabilization ORIF pathologic fractures	Intralesional Intralesional Intralesional
Bone sarcoma	Biopsy for diagnosis Extended intralesional curettage of low-grade chondrosarcoma Resection for cure of most sarcomas	Intralesional Intralesional Wide

Limb Salvage Versus Amputation

The most important goal of the surgical treatment of
bone sarcoma is complete resection of the tumor with a wide margin.
Maximizing function and salvaging the limb are secondary but important
considerations in surgical planning. The decision to perform limb
salvage versus amputation is dependent on several factors.

Indications for Limb-Sparing Surgery

Wide resection (complete resection of the tumor) must be attainable.
Function of the salvaged limb must be at
least as good as the function of the limb after amputation at the
appropriate level required for complete tumor resection (Fig. 4.3-1).
Reconstructed limb must be stable and durable.
There must be adequate skin and soft tissue after resection of the tumor to allow for coverage of the limb/reconstruction.
- Local rotation of tissues and the use of free tissue transfer have broadened the indications for limb salvage.
Usually major neurovascular bundles must not be involved or surrounded by tumor.

Evaluation and Management of Possible Neurovascular Involvement

Magnetic resonance imaging (MRI) is the
gold standard for imaging to determine the relationship of the tumor to
the surrounding structures.
Major vessel resection en bloc with the sarcoma and reconstruction with vein graft or artificial vessel graft is possible.
Resection of major nerves is allowable as
long as the predicted function of the limb is at least as good as an
amputation with prosthesis.
- Upper extremity: As a general rule, any function saved is better than an amputation
- Lower extremity
  - Patients without a sciatic nerve can walk; may require ankle–foot orthosis (AFO) and/or assistive device.
  - Femoral nerve resection/loss of extensor
    mechanism is not an indication for amputation, as patients can walk
    without active knee extension.

Relative Contraindications to Limb Salvage

Displaced pathologic fracture, due to tumor contamination throughout extent of fracture hematoma
- Not absolute, as there is literature to
  support limb salvage after pathologic fracture if there is a good
  response to chemotherapy and the fracture heals
Misplaced biopsy site or prior “nononcologic” procedure performed with contamination of surrounding tissues

Reconstruction of limb not possible to allow function equivalent to an amputation

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Figure 4.3-1
When the expected function following limb preservation is worse than
that following amputation, the latter is preferred, as in this patient
with a Ewing sarcoma of the calcaneus. Preoperative lateral foot
radiograph (A) and sagittal T1-weighted (B) and coronal T2-weighted magnetic resonance images (C) are shown. This patient underwent below-knee amputation (D).

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Poor response to chemotherapy
Vital neurovascular structures encased by tumor and not reconstructible or amenable to bypass

Amputation

Primary goal of amputation, like limb salvage surgery, is to resect the entire tumor with adequate “wide” margins.
Secondary goals of amputation are functional:
- Must result in a stump that will allow for fitting of a prosthesis
- Prosthetic fitting and rehabilitation is
  an important part of recovery and can be difficult while patient is
  still undergoing postoperative chemotherapy.
Risk of surgical complications is lower than for limb-sparing surgery.
- Sometimes required after failed limb salvage attempts (e.g., infection, prosthesis failure, fracture)

Expendable Bone

After determining that limb-sparing surgery is
indicated, the decision of whether to reconstruct or not must be
weighed next. The specific sites of bone that are generally considered
expendable, and therefore not in need of reconstruction, are those
listed.

Fibula: usually no bony reconstruction
required (lateral collateral ligament [LCL] stabilization proximally or
augmentation distally is sometimes required)
Iliac wing: when acetabulum not involved (some surgeons advocate reconstruction to restore pelvic continuity)
Pubis: if hip joint maintained, no bone reconstruction of inferior pelvis usually necessary
Rib: no bone reconstruction necessary
Distal ulna: no bone reconstruction is necessary, but soft tissue repair of the triangular fibrocartilage is recommended (Fig. 4.3-2)

Limb Reconstruction

Generalities of Available Options

There are several options for reconstructing skeletal
defects after resection of malignant or aggressive benign bone tumors.
Each has inherent advantages and disadvantages, and these should be
considered when planning limb salvage surgery. The seven “A’s” of limb
reconstruction are:

Amputation
Autograft
Arthrodesis
Allograft
Arthroplasty
Allograft-prosthetic composites (APC)
Alternative reconstructions

Amputation (see Fig. 4.3-1)

Advantages
- Lowest complication rate
- Least chance of requiring reoperation for failure of reconstruction
Disadvantages
- Body image issues
- Function of upper extremity or proximal lower extremity may be fair to poor.

Figure 4.3-2
This patient underwent resection of the left distal ulna for a
malignant fibrous histiocytoma adjacent to the bone. The distal ulna is
an example of an expendable bone, since it does not require
reconstruction.

Autograft (Fig. 4.3-3)

Vascularized (e.g., free fibula) or nonvascularized (iliac crest, rib, fibula)
Advantages
- “Normal” bone
- Durable reconstruction
- No risk of disease transmission
Disadvantages
- Limited by size of defect and amount of bone available
- Additional morbidity from donor site
- Risk of cross-contamination (small)

Arthrodesis: Fusion of Bone With Elimination of Joint (Fig. 4.3-4)

Advantages
- Stable reconstruction after union
- No need for revision/repeat surgery after union
Disadvantages: does not allow immediate
function/weight bearing, may require additional bone graft (auto- or
allograft), delayed union/nonunion rates can be high depending on site

Allograft

Supplied by “bone bank”: sterilization with or without radiation (weakens), processing required for storage and transplantation

“Rejection” of transplanted bone does not occur, but role of “histocompatibility” is currently being evaluated.

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Figure 4.3-3
These early postoperative radiographs show an autograft nonvascularized
proximal fibula that has been used to reconstruct the defect following
resection of a distal radius for a giant cell tumor of bone. In this
case, the fibula was used to achieve an intercalary arthrodesis. A
proximal fibula may also be used with ligament reconstruction to
replace the distal radius and allow some wrist motion.

Figure 4.3-4 Radiographs of the proximal femur (A) and knee (B).
An extra-articular resection of the distal femur was performed
secondary to extensive tumor extension into the knee joint. An
intercalary allograft fusion of the knee with a long intramedullary
fusion nail was performed.

Intercalary: segment of bone between joints maintained; host joint surfaces maintained; cylinder versus hemi-cylinder (Fig. 4.3-5)
Osteoarticular: articular surface of allograft used to reconstruct at least part of the joint surface (Fig. 4.3-6)
Advantages
- Stable reconstruction after union
- Not limited by size of reconstruction required
- No donor morbidity
Disadvantages
- Infection up to 20%
- Nonunion/delayed union of host–graft junctions up to 20%
- Fracture of allograft up to 15% to 20%
- Disease transmission possible
- Size of allograft needs to be matched to host.

Arthroplasty

Usually by “megaprostheses”; modular endoprosthesis that can replace segments of bone and adjacent joint(s) (Fig. 4.3-7)
Advantages
- Stable reconstruction that usually allows early weight bearing
- Implant failure short term is low (less than fracture, nonunion of allograft)
- No disease transmission
- Size of reconstruction less of a problem (e.g., “total femur” and variable sizing of implant possible)
Disadvantages
- Will likely require (several) revisions over lifetime

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Figure 4.3-5
Intercalary allograft reconstruction of a right proximal humeral
diaphyseal osteosarcoma. Preoperative studies include radiograph (A) and T1-weighted sagittal (B) and T2-weighted sagittal (C) magnetic resonance images. (D)
Postoperative radiograph shows dual 90:90 plate fixation spanning the
intercalary allograft, which is filled with antibiotic-loaded cement.

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Figure 4.3-6
Following resection of a giant cell tumor of the distal radius, this
patient underwent reconstruction using a distal radius osteoarticular
allograft.

Figure 4.3-7
Lateral radiograph of the knee shows a rotating-hinge distal femoral
replacement endoprosthesis. Both the femoral stem and tibial stem are
cemented. The surgical clips are seen that were used to ligate the
multiple branches off the popliteal artery at the time of resection of
this distal femur osteosarcoma.

Allograft-Prosthetic Composite (APC)

Combines segmental reconstruction of bone
with allograft and joint surface reconstruction with more standard
arthroplasty (cemented) components (Fig. 4.3-8)
Advantages
- May allow for
  better soft tissue (tendon) attachment about the joint and therefore
  more stability (e.g., host rotator cuff to proximal humeral APC or host
  patellar tendon to proximal tibial APC or host gluteus medius tendon to
  proximal femoral APC)
- Some surgeons believe this allows better function of that joint (controversial).
Disadvantages
- Technically more difficult
- All the risks of allograft and
  arthroplasty combined, though stems of prosthesis should cross host
  allograft junction to make nonunion and fracture less of a clinical
  problem
- Disease transmission

Alternative Reconstructions

Site-specific options may have advantages over other types of reconstructions.
- Rotationplasty: for resections about the knee (Fig. 4.3-9)
- Single-bone forearm after radial/ulnar tumor resection (Fig. 4.3-10)
- Bone transport/limb lengthening
- Physeal distraction in children

Reconstruction in the Growing Child

Since bone sarcomas can occur at ages where there is
more bone growth left, resection of bone can result in significant leg
length discrepancies. This needs to be considered in the treatment of
these young patients. One indication for amputation is significant limb
length inequality after treatment. However, options do exist for limb
salvage surgery in growing children:

Expandable prostheses can be “lengthened” as the child grows (Fig. 4.3-11).

Rotationplasty requires preoperative planning to achieve both knees being at same level at skeletal maturity (see Fig. 4.3-9).

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Figure 4.3-8 After resection of an acetabular sarcoma, an allograft–prosthetic composite of the acetabulum was used for reconstruction. (A)
An anteroposterior (AP) radiograph soon after surgery shows the
acetabular cage and constrained cup cemented into the acetabular
allograft and the cemented femoral stem. The allograft is secured with
interfragmentary lag screws and pelvic reconstruction plates. (B) The allograft–host junctions are healed at 9 months postoperatively.

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Figure 4.3-9
A postoperative picture of a skeletally immature patient after
rotationplasty was performed following extra-articular resection of a
distal femur osteosarcoma. The tibia has been turned 180 degrees and
osteosynthesis between the proximal femur and proximal tibia was
performed. The sciatic nerve and femoral arteries and veins were
preserved, as was active motion at the ankle. This allowed what would
have been an above-knee amputation to potentially function as a
below-knee amputation.

Limb lengthening after treatment (e.g., bone transport or Ilizarov technique)
Claviculo-pro-humero (autograft clavicle used to replace proximal humerus)
Proximal fibular autograft

Location-Specific Reconstructive Options

There are unique anatomic considerations to each site of
bone tumor resection. Those, along with the reconstructive options, are
discussed below.

Scapula (Fig. 4.3-12)

Many patients with scapular bone sarcomas undergo
resection without reconstruction, but scapular endoprostheses are
available; proponents cite improved functional outcome through
lateralization of the shoulder joint.

Unique anatomic considerations
- Soft tissue extent determines feasibility of scapular endoprosthetic reconstruction.
Reconstructive options
- Flail shoulder reconstruction
- Scapular endoprostheses (see Fig. 4.3-12)
  - Need rhomboids, trapezius, latissimus dorsi, serratus anterior, some of rotator cuff

Proximal Humerus (Figs. 4.3-13 and 4.3-14)

Unique anatomic considerations
- Intra-articular involvement
  - Some surgeons feel the shoulder joint should be routinely resected en bloc with the proximal humerus due to a purported high incidence of intra-articular tumor extension.
  - Many surgeons feel the resection should be based upon individual radiographic assessment.
- Rotator cuff tendon insertion at tuberosities
  - Any resection of the proximal humerus
    entails sacrifice of the native rotator cuff attachments, and only
    osteoarticular allograft and allograft prosthetic composite
    reconstructions allow the potential for suturing of the host tendons to
    the reconstruction.
- Axillary nerve and deltoid muscle insertion at deltoid tuberosity
  - Axillary nerve and/or deltoid muscle resection is sometimes needed for tumor resection based upon soft tissue extension.
  - Without the axillary nerve and/or deltoid function, the best reconstructive options are arthrodesis or proximal humeral spacer.
  - If axillary nerve and deltoid function
    can be preserved, mobile reconstructive options (osteoarticular
    allograft, allograft prosthetic composite, and megaprosthesis) are
    viable alternatives.
- Glenohumeral joint stability
Reconstructive options (Table 4.3-2)
- Osteoarticular allograft
- Allograft prosthetic composite (see Fig. 4.3-13)
- Proximal humeral megaprosthesis (see Fig. 4.3-14)
- Proximal humeral spacer prosthesis (Fig. 4.3-15)

Humeral Shaft (Figs. 4.3-5 and 4.3-16)

Unique anatomic considerations

Deltoid muscle insertion at deltoid tuberosity
- Remaining deltoid may be sewn to allograft soft tissue or to a sleeve of synthetic material around prosthesis.

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Figure 4.3-10
Single-bone forearm reconstruction following resection of a proximal
radial osteosarcoma. Preoperative studies include AP and lateral
radiographs (A,B) and an axial T1-weighted magnetic resonance image (C). (D,E) Postoperative AP and lateral radiographs.

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Figure 4.3-11 (A,B)
In this skeletally immature patient with a proximal tibial Ewing
sarcoma, the tibia was reconstructed using an expandable prosthesis,
maintaining the distal femoral physis. (C)
This specific expandable prosthesis has a deformable resin, which, when
placed in a magnetic coil, allows expansion of the encased preloaded
spring device. The expansion procedure does not require a skin incision.

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Figure 4.3-12 This patient with Ewing sarcoma of the right scapula shown on plain radiograph (A) and T1-weighted (B) and T2-weighted (C) axial magnetic resonance images underwent scapulectomy and prosthetic scapular reconstruction (D), maintaining the integrity of the proximal humeral metaphysis following neoadjuvant chemotherapy.

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Figure 4.3-13 A proximal humeral osteosarcoma (A) has been reconstructed using an allograft–prosthetic composite reconstruction (B,C).
The intraoperative photo shows dual 90:90 plate fixation of the
allograft and sutures being used to repair the host rotator cuff to the
allograft rotator cuff (C).

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Figure 4.3-14 This patient with metastatic renal carcinoma to the right proximal humerus (A)
underwent resection and reconstruction using a proximal humeral
replacement endoprosthesis, shown here intraoperatively prior to
reduction and closure (B).

Reconstructive options (Table 4.3-3)
- Intercalary allograft (see Fig. 4.3-5)
- Intercalary metallic spacer (see Fig. 4.3-16)

Distal Humerus

Unique anatomic considerations
- Elbow joint
  - Use of osteoarticular allografts in this
    site is usually limited to partial distal humeral resections and
    requires soft tissue repair.
Reconstructive options (Table 4.3-4)
- Distal humeral osteoarticular allograft
- Custom distal humeral megaprosthesis total elbow replacement
Rehabilitative considerations
- Early range of motion is crucial to maximize function.

Table 4.3-2 Reconstructive Options for the Proximal Humerus

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Osteoarticular allograft	Allows rotator cuff repair	Potential for late subchondral collapse
Allograft prosthetic composite	Allows rotator cuff repair		Eliminates potential for subchondral collapse
Proximal humeral megaprosthesis	Less technically difficult	No rotator cuff repair Potential instability	Potential for shoulder function controversial
Proximal humeral spacer prosthesis	Less technically difficult	No rotator cuff repair Potential instability	Only provides stable post for distal function
Intercalary allograft arthrodesis	Stable, durable function achieved	Technically very difficult May require vascularized fibula graft	Scapulothoracic motion preserved

Distal Radius (see Figs. 4.3-3 and 4.3-6)

Unique anatomic considerations
- Wrist joint instability
Reconstructive options
- Mobile wrist reconstruction (see Fig. 4.3-6)
- Wrist fusion (see Fig. 4.3-3)

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Figure 4.3-15
A proximal humeral spacer prosthesis has been cemented into the
remaining humerus and used to suspend the limb to the chest wall
following an extensive resection of the shoulder girdle, including the
deltoid musculature. In this case, the prosthesis helps to provide a
stable post for distal upper extremity function, but essentially no
shoulder function is achieved.

For each of the reconstructions, either an allograft or
the proximal fibula may be used. Mobile wrist reconstructions require
meticulous soft tissue repair to avoid instability. Proximal fibular
grafts rarely need to be vascularized, as the total length of the graft
needed is rarely long enough to encompass the region where the vascular
supply enters the proximal fibula. The lateral collateral ligament must
be repaired at the donor site.

Periacetabular Region

Unique anatomic considerations
- Hip joint instability
Reconstructive options (Fig. 4.3-8 and Table 4.3-5)
- Resection arthroplasty (flail hip reconstruction)
- Hip arthrodesis (ischiofemoral or
  iliofemoral, depending upon resection and remaining bone; with or
  without intercalary allograft)
- Allograft prosthetic composite total hip replacement (see Fig. 4.3-8)
- Saddle prosthesis
Rehabilitative considerations
- Period of bracing (hip abduction orthosis) to allow for soft tissue healing used by some surgeons routinely
- Weight bearing may be delayed to allow for healing of the allograft–host junction in a composite reconstruction.

Proximal Femur (Fig. 4.3-17)

Unique anatomic considerations
- Gluteus medius tendon insertion
  - Level of tendon resection dictated by soft tissue extent of tumor
  - Even for completely intraosseous sarcoma,
    approximately 2-cm cuff of tendon generally left with resected femur to
    achieve wide margin
- Hip joint instability
  - Degree of instability dependent on extent
    of bone and soft tissue resection, including capsule, hip abductor,
    iliopsoas, and adductors
  - Standard soft tissue closure should attempt to restore stability.
    - Bipolar components generally considered more stable than total hip arthroplasty
    - Cerclage closure of remaining capsule when remains
    - Synthetic substitution when no remaining capsule (synthetic aortic grafts commonly used)
    - Gluteus medius tendon reefed into
      allograft tendon, abductor attachment device on prosthesis, and/or
      vastus lateralis muscle when feasible
Reconstructive options (Table 4.3-6)
- Allograft–prosthetic composite
- Proximal femoral megaprosthesis (see Fig. 4.3-17)
Rehabilitative considerations same as for periacetabular region

Femoral Shaft

Reconstructive options (Table 4.3-7)
- Intercalary femoral allograft
- Custom intercalary femoral metallic spacer
Rehabilitative considerations
- Intercalary femoral allograft
  reconstruction requires prolonged period of limited weight bearing
  until radiographic signs of healing evident.
- Cemented custom intercalary femoral spacer allows immediate full weight bearing.

Distal Femur (Fig. 4.3-18)

Unique anatomic considerations

Ligamentous stability of knee joint
- Most easily substituted for by use of
  rotating hinge knee components (fully constrained), but this increases
  stresses at bone–cement or bone–prosthesis (for cementless) stemmed
  components
- Use of allograft–prosthetic composite
  reconstruction with repair of allograft–host collateral ligament(s) or
  capsule may allow use of a less constrained device than a hinge
  (usually a constrained condylar type).

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Figure 4.3-16
Intercalary humeral metallic spacers have been used predominately for
reconstruction of segmental diaphyseal defects in patients with
metastatic carcinoma and myeloma. (A) The radiograph shows the early male–female taper device with both components cemented and reduced. (B) This intraoperative photograph shows the current lap joint with Morse taper and compression set screw.

Table 4.3-3 Reconstructive Options for the Humeral Shaft

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Intercalary allograft	Biologic reconstruction Allows deltoid repair	Allograft fracture Allograft-host nonunion Higher infection risk	Higher fracture risk with plate/screws Higher nonunion risk with intramedullary fixation
Intercalary metallic spacer	Immediate stability Avoids allograft risks	Less durable	Usually reserved for patients with limited life expectancy

Table 4.3-4 Reconstructive Options for the Distal Humerus

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Distal humeral osteoarticular allograft	Biological reconstruction	Allograft fracture Allograft-host nonunion Infection risk	Extremely difficult to achieve size matching
Custom distal humeral megaprosthesis	Avoids allograft risks	Potential for aseptic loosening	Usually custom component required

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Table 4.3-5 Common Reconstructive Options for the Periacetabular Region

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Resection arthroplasty	Minimizes complications	Least potential functional outcome
Hip arthrodesis	Stable hip	Technically demanding Difficult to achieve union	Intercalary allograft more common for iliofemoral fusion
Allograft-prosthetic composite	Best potential functional outcome	Extremely high risk: instability, allograft fracture, allograft-host nonunion, infection	Cement cup into allograft acetabulum
Saddle prosthesis	Stable hip but preservation of some motion	May dislocate from iliac notch	Mersilene tape through drill holes in ilium often used to increase initial stability

Figure 4.3-17 A proximal femoral Ewing sarcoma (A) was treated with neoadjuvant chemotherapy followed by resection and reconstruction with a proximal femoral prosthesis (B). (C) Intraoperative photos show the prosthesis in place with the bipolar component reduced in the acetabulum. (D)
Sutures attached to the remaining hip abductors proximally and to the
vastus lateralis distally have been pulled in the direction of closure.
When possible, these structures are reefed together and may be attached
to the prosthesis with tape or nonabsorbable suture.

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Table 4.3-6 Common Reconstructive Options for the Proximal Femur

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Allograft-prosthetic composite	Allows reattachment of hip abductors Potential improvement in hip abductor function Potential improvement in hip stability	Allograft fracture Allograft-host nonunion Infection risk PLUS all of prosthetic risks	Bipolar components favored for stability Capsular reconstruction beneficial
Proximal femoral megaprosthesis	Avoids allograft risks	Hip instability Aseptic loosening

Reconstructive options (Table 4.3-8)
- Allograft–prosthetic composite
- Distal femoral megaprosthesis (see Fig. 4.3-18)
Rehabilitative considerations
- Many surgeons rehabilitate these patients
  similar to a standard total knee replacement, with early weight bearing
  for cemented components and early aggressive range of motion.
- Weight bearing may be delayed to allow for healing of the allograft–host junction in a composite reconstruction.

Proximal Tibia (Figs. 4.3-19 and 4.3-20)

Unique anatomic considerations
- Patellar tendon insertion/extensor mechanism
  - Level of reconstruction is dictated by
    level of resection and may be through the patellar tendon (most
    common), transpatellar, or through the quadriceps tendon.
  - Level of resection is dictated by tumor extent.
- Limited native soft tissue coverage
  - Medial gastrocnemius muscle flap is used by many surgeons for routine coverage of reconstruction.
Reconstructive options (Table 4.3-9)
- Allograft–prosthetic composite (see Fig. 4.3-19)
- Proximal tibial megaprosthesis (see Fig. 4.3-20)
Rehabilitative considerations are same as for distal femoral reconstruction.

Tibial Shaft (Fig. 4.3-21)

Unique anatomic considerations
- Limited native soft tissue coverage
Reconstructive options (Table 4.3-10)
- Intercalary allograft (see Fig. 4.3-21)
- Fibular interposition graft (single or double barrel)
- Custom tibial metallic prosthesis

Table 4.3-7 Common Reconstructive Options for the Femoral Shaft

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Intercalary femoral allograft	Biological reconstruction	Allograft fracture Allograft-host nonunion Infection risk	Higher fracture risk with plate fixation Higher nonunion risk with intramedullary fixation
Custom intercalary femoral metallic spacer	Avoids allograft risks	Less durable Usually reserved for patients with limited life expectancy	Usually available only on custom basis

Distal Tibia (see Fig. 4.3-1)

Most patients with high-grade distal tibial bone
sarcomas warrant below-knee amputation for the prime reason that
function is better with the use of a prosthesis than after
reconstruction.

Unique anatomic considerations
- Ankle joint
- Soft tissue coverage of distal third of leg
  - Free-flap coverage should be considered.
  - Too distal for soleus flap

Reconstructive options

Distal tibial allograft–arthrodesis

May be accomplished with retrograde
intramedullary nail fixation through calcaneus, talus, and across
intercalary segmental allograft into proximal host bone

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Figure 4.3-18 A distal femoral osteosarcoma is shown on an AP plain radiograph (A) and sagittal fat-suppressed inversion recovery magnetic resonance image (B). (C,D)
After preoperative chemotherapy and resection, the distal femur was
reconstructed using a distal femoral megaprosthesis rotating hinge knee
replacement. Postoperative radiographs also show screw fixation of a
slipped capital femoral epiphysis, which occurred during postoperative
chemotherapy.

Table 4.3-8 Common Reconstructive Options for the Distal Femur

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Allograft-prosthetic composite	Partial biological reconstruction May allow less constrained total knee to be used	Allograft fracture Allograft-host nonunion Infection risk Technically more difficult	Long-stem femoral component should bypass allograft-host junction
Distal femoral megaprosthesis	Avoids allograft risks Technically easier	Aseptic loosening

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Figure 4.3-19 Intraoperative photographs during a proximal tibial allograft–prosthetic composite reconstruction. (A) The allograft has been prepared on the back table, and the trial tibial component has been placed through the bone. (B) The rotating hinge tibial and femoral components have been cemented into place. (C) The host and allograft patellar tendons have been sutured together. (D)
Finally, the medial gastrocnemius muscle flap has been closed over the
construct in preparation for split-thickness skin grafting.

Prolonged limited weight bearing needed until signs of allograft–host healing
Normal allograft risks apply: fracture, delayed union, nonunion, and infection

Chemotherapy

Prior to 1970, the 5-year survival of patients with
nonmetastatic osteogenic sarcoma treated with surgical ablation of the
tumor was less than 20%. The primary mechanism of failure for these
patients was the development of fatal pulmonary metastases. In the
1970s, the benefit of adjuvant chemotherapy started to emerge, with
individual institutional protocols reporting increased survival in
patients treated with both surgery and chemotherapeutic agents.
Unfortunately, early trials provided conflicting results and confusion.
As a result, two prospective randomized trials were designed to define
the role of adjuvant chemotherapy in the treatment of osteosarcoma.
Both the Multi-Institutional Osteosarcoma Study Group and the UCLA
group unequivocally demonstrated that the addition of chemotherapy to
surgical excision of the tumor significantly improved survival. In the
modern era, standard treatment for nonmetastatic osteogenic sarcoma
consists of a combination of chemotherapy and surgery resulting in
5-year survival rates of 60% to 65%. Ewing sarcoma enjoys similar
survival statistics when chemotherapy is used along with local control.

Indications/Contraindications

Indications

Chemotherapy has been shown to be effective in improving survival for the majority of malignant bone tumors:

Osteogenic sarcoma (high-grade conventional)
Ewing sarcoma
Malignant fibrous histiocytoma of bone
Fibrosarcoma of bone
Leiomyosarcoma of bone
Lymphoma of bone

Relative Contraindications

High-grade chondrosarcoma
- Some have advocated chemotherapy for the spindle
  
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  cell component of dedifferentiated chondrosarcoma and for mesenchymal
  chondrosarcoma, though no improvement in survival has ever been
  demonstrated.

Figure 4.3-20
A proximal tibial endoprosthetic reconstruction following resection of
an osteosarcoma. Preoperative anteroposterior radiograph (A) and coronal T1-weighted magnetic resonance image (B). (C)
Intraoperative photograph shows the cemented proximal tibial
megaprosthetic rotating hinge total knee replacement in place. The
remaining host patellar tendon has been sutured with Mersilene tape to
the polished loop prior to coverage with the medial gastrocnemius flap,
which has been mobilized and is laid back medially (top) in this figure.

Table 4.3-9 Common Reconstructive Options for the Proximal Tibia

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Allograft-prosthetic composite	Partial biological reconstruction Allows repair of host-allograft patellar tendon or through patellar osteotomy	Allograft fracture Allograft-host nonunion Infection risk Technically more difficult	Long-stem tibial component should bypass allograft-host junction
Proximal tibial megaprosthesis	Avoids allograft risks Technically easier	Doesn’t allow biologic repair of extensor mechanism

Absolute Contraindications

Nonmetastatic low-grade sarcomas (no role for chemotherapy)
- Low-grade parosteal osteogenic sarcoma
- Low-grade central osteosarcoma
- Low-grade chondrosarcomas

Chemotherapeutic Drugs

In general, chemotherapy works by damaging DNA or
halting the cell cycle. It preferentially targets rapidly dividing
cells, those of both high-grade tumors and normal cells with high
division rates. Affected normal cells manifest some of the commonly
seen side effects from chemotherapy: alopecia from hair follicles,
mucositis from gastrointestinal mucosa, and myelosuppression from the
hematopoietic system. Fortunately, great strides have been made in
supportive measures to decrease the intensity of adverse side effects,
thereby allowing for clinically effective chemotherapeutic dosing (Table 4.3-11).

Figure 4.3-21 (A)
A lateral postoperative radiograph of the tibia shows an intercalary
allograft fixed with multiple plates and screws. Graft–host junctions
are still visible. (B) A radiograph
obtained 9 months after surgery reveals complete healing of the
proximal and distal graft junctions. The patient obtained near-normal
postoperative function of the ipsilateral ankle and knee joints.

The best outcomes in bone sarcoma treatment are
associated with multiagent or combination chemotherapy as opposed to
single-agent regimens. Most patients with malignant bone tumors are
treated in the setting of a clinical trial or on established protocols.
Table 4.3-12 outlines the most commonly used
chemotherapy agents for specific malignant bone tumors. While there is
some institutional variability

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for
a given tumor, the tumor cytotoxicity of the drugs listed below has
been well established. The exact drugs, duration, and dosing used
remain controversial.

Table 4.3-10 Common Reconstructive Options for the Tibial Shaft

Reconstructive Option	Advantages	Disadvantages	Unique Issues
Intercalary tibial allograft	Biological reconstruction	Allograft fracture Allograft-host nonunion Infection risk	Higher fracture risk with plate fixation Higher nonunion risk with intramedullary fixation Sometimes combined with vascularized fibular grafts to facilitate healing
Fibular interpositional graft	Autogenous biological reconstruction	Donor site morbidity	Fibular grafts hypertrophy over time
Custom intercalary tibial metallic spacer	Avoids allograft risks	Less durable Usually reserved for patients with limited life expectancy	Usually available only on custom basis

Important Chemotherapy Concepts

Induction Chemotherapy

Definition: chemotherapy administered before gross total resection of the tumor
- Synonyms: neoadjuvant or preoperative chemotherapy
Historical perspective: Originally
administered during the advent of limb salvage surgery in order to
treat patients while custom prostheses were being manufactured
Advantages
- Immediate treatment of micrometastases and potential metastatic sites
- Reduces surrounding tumor edema and in some instances shrinks the tumor, facilitating surgical resection
- Causes tumor necrosis, providing important prognostic information (see Assessment of Chemotherapy Response below)
While induction chemotherapy has become
the standard of care for osteogenic sarcoma and Ewing sarcoma, the
administration of chemotherapy prior to surgical removal of the tumor
has never been shown to improve patient survival.

Table 4.3-11 Biologic Response Modifiers Used to Treat Chemotherapy Toxicities

Protective Agent	Use
Dexrazoxane	Cardiac
Erythropoietin	Anemia
Granulocyte colony-stimulating factor (G-CSF)	Neutropenia
Leucovorin	Rescue normal cells from methotrexate effects
Mesna	Hemorrhagic cystitis

Pathologic Assessment of Chemotherapy Response

Aside from the presence of metastatic
disease at presentation, histologic necrosis following induction
chemotherapy is the most powerful predictor of disease-free survival
available.
- Synonyms: Huvos grading system
Prognostic value has been established for both osteogenic sarcoma and Ewing sarcoma.
Calculated by quantifying tumor viability on grid constructed from cut sections of the tumor (Fig. 4.3-22)
Theoretically, the amount of necrosis reflects the effectiveness of the therapy.
Consists of a four-tiered grading system
- Grade I (0% to 50% necrosis)
- Grade II (51% to 90% necrosis)
- Grade III (91% to 99% necrosis)
- Grade IV (100% necrosis)
Clinical significance
- “Good response” (grade III and IV) is associated with superior survival outcomes (as high as 89% at 5 years).
- Grade I and II responders are at increased risk of relapse.
  - A grade I response is superior to no chemotherapy (5-year survival of 50% versus 17%, respectively).
- Increasing necrosis by prolonging
  chemotherapy induction time or dose intensification does not correlate
  with increased survival (i.e., the grading system loses its prognostic
  power).

Clinical and Radiographic Assessment of Chemotherapy Response

Decreased pain and swelling

Decreased alkaline phosphatase

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Table 4.3-12 Chemotherapy Agents Used to Treat Malignant Bone Tumors

Sarcoma Type	Commonly Used Chemotherapy Agents	Mechanism of Action	Associated Major Toxicity
Osteogenic sarcoma	Doxorubicin	Binds DNA via intercalation on the DNA helix, blocking DNA and RNA synthesis Inhibits topoisomerase II Produces free radicals, cleaving DNA and the cell membrane	Cardiomyopathy, myelosuppression
	Cisplatin	Covalently binds DNA, disrupting DNA function	Renal failure, neuropathy, ototoxicity, myelosuppression
	High-dose methotrexate	Inhibits dehydrofolate reductase, thereby blocking thymidine synthesis and hence DNA synthesis	Mucositis, renal toxicity
	Ifosfamide	Alkylates DNA, leading to cross-linking	Cystitis, renal failure, encephalopathy
Ewing sarcoma	Vincristine	Prevents the polymerization of tubulin to form microtubules, thereby blocking mitosis	Peripheral neuropathy
	Doxorubicin	Binds DNA via intercalation on the DNA helix, blocking DNA and RNA synthesis Inhibits topoisomerase II Produces free radicals, cleaving DNA and the cell membrane	Cardiomyopathy, myelosuppression
	Cyclophosphamide	Alkylates DNA, leading to cross-linking	Cystitis, renal failure, encephalopathy
	Ifosfamide	Structural analogue of cyclophosphamide with same mechanism of action	Same as cyclophosphamide
	Etoposide	Inhibits DNA topoisomerase II, thereby inhibiting DNA synthesis	Neutropenia
Malignant fibrous histiocytoma, fibrosarcoma, and leiomyosarcoma of bone	Same as for osteogenic sarcoma
Lymphoma (also see Chapter	CHOP (cyclophosphamide, hydroxydoxorubicin, Oncovin [vincristine], prednisone)	See above

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Figure 4.3-22 Pathologic assessment of chemotherapy response. (A) Gross photograph of a distal femoral osteogenic sarcoma. (B) Mapping of the gross specimen for histologic analysis.

“Normalization” of the tumor on x-ray (Fig. 4.3-23)
Decreased uptake on Tc-99 bone scan and thallium scan
Decreased edema on magnetic resonance imaging (Fig. 4.3-24)
Decreased size of the tumor
- Most commonly seen in Ewing sarcoma
- Seldom seen in osteogenic sarcoma secondary to osteoid matrix

Chemotherapy Tailoring

Definition: Refers to modifying the postoperative chemotherapy regimen for an inferior histologic response to chemotherapy
Most studies have failed to increase survival by changing or intensifying chemotherapeutics.

Radiation Therapy

Radiation therapy is a local treatment modality. The
most commonly used form of radiotherapy is a high-energy photon beam
delivered by a linear accelerator. When the beam collides with its
target, it “ionizes” its target by removing an orbiting electron from
an atom or group of atoms. In tumors, the target is water in the tumor
cells, which creates highly reactive free radicals capable of causing
DNA stand breaks and eventually cell death. For bone tumors, radiation
is usually delivered as fractionated (small doses) external beam
radiation administered on consecutive days for a specified period of
time. Fractionation allows for a large total dose to be delivered
without exceeding the threshold of the normal surrounding tissues.

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Figure 4.3-23 Normalization of the tumor following induction chemotherapy. (A) Preoperative x-ray of a diaphyseal femoral osteogenic sarcoma demonstrating periosteal elevation with soft tissue extension. (B) Following induction chemotherapy, there is increased sclerosis in the femur and thickening of the periosteum.

Dosage

Radiation dose is typically reported as the absorbed dose, which is measured in grays (Gy).

1 Gy = 1 J/kg
1 centigray (cGy) = 1/100 of a Gy
1 rad = 1 cGy

For bone tumors, a total dose of 4,500 to 6,000 cGy is
delivered in fractionated doses of 180 to 200 cGy per day, 5 days per
week.

While the role of radiation is well established in the
management of soft tissue sarcomas, it has a less defined role in the
management of bone malignancies.

Figure 4.3-24 MRI assessment of chemotherapy response. T1-weighted fat-suppressed MR images of an osteogenic sarcoma of the proximal tibia. (A) Considerable edema surrounds the tumor at presentation. (B) The same tumor following 9 weeks of induction chemotherapy.

Use in Specific Tumors

Osteogenic Sarcoma

Very limited role for radiation
Primary indications
- Anatomic locations where complete surgical resection is not feasible
- Palliate symptomatic metastases

Ewing Sarcoma

Very radiosensitive
Radiation is a standard local control option, achieving local control rates of greater than 70%.
Overall survival is similar for patients treated with radiation compared to surgery.

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Local recurrence rate is likely greater in irradiated patients compared to surgically treated patients.
Primary indications
- When surgical treatment would cause unacceptable disfigurement, functional deficit, morbidity, or mortality
- When surgical margins are positive or close
- Metastases

Chondrosarcoma

Radioresistant
May have a role to palliate unresectable tumors

Chordoma

Definitive local control has been
reported with highly conformal therapy such as high-dose
proton/photon-beam radiation and intensity-modulated radiation therapy
(IMRT).
Requires very high doses (>7,000 cGy) to maximize local control
For large tumors, preoperative radiation may facilitate surgical resection.
Postoperative radiation has been associated with improved local control.

Lymphoma of Bone

Used as the primary local control measure

Side Effects

Dermatologic
- Acutely: erythema, desquamation, wound dehiscence
- Long-term: hyperpigmentation
Myelosuppression (acutely)
Muscle fibrosis
Extremity edema
Joint contractures
Growth arrest
Fracture
Avascular necrosis
Secondary malignancy
- Requires a latency period of at least 3 years, though typically occurs 10 to 20 years after radiation
- Risk is ~1% following treatment for all childhood cancers.
- Risk is ~5% following treatment for Ewing sarcoma.