MBD of extremities. as difficult it is to find.. here is slides to explain about MBD

1. Metastatic Bone Disease
Oncology team
TM / MC
Supervisor : dr. Dewi Kurniati, M.Kes, Sp.OT

2. Case report

3. What is MBD ???
• metastases, is a natural progression of a variety of malignancies.
• They have variable 1mode of spread, 2manner of presentation,
3prognosis, depending on the primary source
• MBD or metastatic bone disease, is the spreading of tumor, from their
primary source, to the bone.
• Skeletal metastases itself is seldom dangerous / life threatening, and
the treatment will most likely do nothing on the primary disease
• Typically a hematogenous proccess

4. • Skeletal metastases is the 3rd most common site for metastases,
behind liver and lung metastases.
• Most frequent places are (in order):
• Thoracic spine
• Ribs
• Pelvis
• Proximal long bones (least common)
• Bone metastases may cause :
• Pain ( either from pathologic fracture or impending pathologic fracture)
• Inhibition of function
• Decreased quality of life

6. • 8-29% patients with MBD will experience pathologic fracture, with
femur as the most common site of the fractures.
• MBD may originate from any of these source :
• Thyroid
• Breast
• Lung
• Renal
• prostate

7. • A recent study by Kirkinis et al in 2016 shows the variations of
originating primary bone tumors found on their patient with MBD

8. Evaluation of patient
• Usually patient with greatest risk of skeletal MBD is from the adult to
elderly population
• Progressive pain is the most common presentation for bone lesions
caused by metastases, or pain from pathologic fracture
• Pain may be
• out of proportion
• Not resolving with symptomatic treatment
• Occurs with weight bearing, at rest and even at night

9. • Other symptoms may include :
• Hypercalcemia, due to osteolytic bone metastases (up to 20% of all osteolytic
bone metastases)
• Myelophtisis, or symptomatic anemia caused by infiltration of metastatic
tumor cells to bone marrow, which may lead to pansitopenia
• Other symptoms not related to this discussions are :
• Nerve root compression due to impingement by bone metastases
• Spinal cord compression due to pathological vertebral collapse or direct epidural
extension

10. How does MBD works ??

13. How does MBD works ??
2 pathways :
•Hematogenous spread
•Local invasion

14. Vascular spread hypothesis
Tumor cells follow circulatory route draining from the primary tumor
and arrest / stop nonspecifically in the first organ encountered
Lung and breast cancer cells  azygos vein  plexus of batson
Thoracic region MBD
Prostrate cancer cells  drainage of blood to pelvic plexus
Lumbosacral spine & pelvis MBD

15. 1. Tumor cell intravasation
E cadherin cell adhesion molecule on
tumor cells modulates release from
primary tumor to bloodstream
2. PDGF promotes tumor migration
3. Chemokine ligand 12 (CXCL12) in
stromal cells bone marrow acts as
homing chemokine, attracting
tumor cells
4. Use matrix metalloproteinases
(MMP) to invade basement
membrane and extracell matrix
5. Induction of angiogenesis

16. Activation of bone lysis
• Tumor cells release IL 6, IL 11, PTHrP,
TGF beta  activate osteoblast.
• Osteoblas secrete RANKLs, binding
with RANK in osteoclast  activating
osteoclast

17. Activation of bone sclerosis
• Cancer cells secrete endothelin 1 (ET1)
• ET 1 binds endothelin A receptor on osteoblast, stimulating it,
• ET 1 decrease WNT suppressor DKK 1  further increasing osteoblast activity

18. Other pathogenesis hypothesis
Seed and soil phenomenon by Stephen paget  somewhat
controversial and not universally accepted
Seed  tumor cells
Soil  organ microenvironment
• The seed grew preferentially in the microenvironment of select
organs (the soil) and metastases resulted only when appropriate seed
was implanted in suitable soil

19. Evaluation of MBD
Imaging studies
• X rays
• CT
• MRI
• Nuclear medicine – technetium bone scan
Lab studies
• Complete blood count
• Erithrocyte sedimentation rate
• LFT, Ca, phosphate, alkaline phosphatase
• SPEP, UPEP

20. Evaluation of MBD
Biopsy
• When primary carcinoma is unknown, a biopsy should be undertaken
to exclude primary bone lesion
Or
• When histologic confirmation of metastatic disease is needed, where
clinical or radiological features are in doubt
• Possibility of new primary bone tumor on an already existing primary
tumor with MBD
Methodes include : bone marrow aspiration or trephine biopsy and CT
guided biopsy sample

21. Treatment…
• 3 ways to cure : 1preventive, 2curative and 3palliative
• Ultimate goal of musculoskeleteal treatment of skeletal metastases is
to get the patient back to his / her previous level of function (if
possible), ASAP!!!
• Skeletal metastases itself is seldom dangerous / life threatening, and
the treatment will most likely do nothing on the primary disease
• OUR early approach may help maximize functional independence and
quality of remaining life to the patient

22. What is our goals?
• 4 main consideration of treatment
• Pain relief
• Preservation or restoration of function
• Skeletal stabilization
• Local tumor control

23. • A multidisciplinary approach is necessary, with comprehensive planning from a
cancer board. Here are the list of who should be in the board and what should
be discussed in the board, taking into consideration, the status of primary
cancer, prognosis and background of the patient

25. Scoring system we can use to predict impending
pathologic fracture
• Mirels classification is a system used to predict the highest risk of
pathological fracture among bones affected by metastases
• Score >8 suggest required prophylactic fixation
• Sensitivity ~90%, specificity ~35% : high ability to predict fracture, but
the location is unknown  may lead to unnecessary fixations

26. Scoring system we can use to predict impending
pathologic fracture
• Risk factors for pathological femoral metastases were also found by a
post hoc analysis of prospective randomized trial of radiotherapy,
stating that :
• Axial cortical involvement >30mm
• Circumferential cortical involvement >50%
Significant predictive factors of fractures
This is somewhat more reliable than Mirels scoring system (for
predicting femoral pathologic fracture)

27. Fixation of fractures with MBD
• Main goals for fracture fixation is :
• Patient survive operation
• Immediate full weight bearing
• Implant survival > patient survival
• All post operative patient require post op radiation
• Should include entire fixation device
• Pre operative embolization is needed in very vascular primary cancer
(eg : thyroid carcinoma, renal cell carcinoma)

30. What do we say to the patient?
• In general, patient with MBD have poor prognosis
• There are several methods which we may use to helo determine the
survival rate of the patient

31. • The same study also found several valuable information which may help in determining
prognosis for the patient.
• In general, the higher the number of interval, the worse the prognosis for the patient

32. Q’s..
• See how you fare through these questions..

33. Q’s..
A 65-year-old patient without a history of cancer presents with thigh
pain and a lytic lesion in the left femur. A CT scan of the chest,
abdomen, and pelvis as well as a bone scan show this to be an isolated
tumor. Biopsy confirms adenocarcinoma. What is the most likely
primary source of this patient's tumor?
1. Gastrointestinal
2. Lung
3. Kidney
4. Prostate
5. Breast

34. Q’s..
• PREFERRED RESPONSE 2
• Occult lytic metastatic adenocarcinoma to bone without an identified primary source after bone
scan and CT of the chest, abdomen, and pelvis is most commonly of lung origin. CT of the
chest/abdomen/pelvis correctly identifies the primary tumor in greater than 90% of cases.
Rougraff et al discuss the diagnostic dilemma of unknown metastatic lesions in 40 patients and
the diagnostic steps used to identify the primary tumor source. Their recommendations include
history, physical exam, routine laboratory analysis, plain radiographs of the entire bone, chest x-
ray, whole-body technetium 99 scan, CT of chest/abdomen/pelvis, and finally biopsy. Their series
indicates that occult metastatic lesions not identified on routine staging studies were most likely
of lung origin. While each diagnostic strategy identified the primary source in some patients, the
CT of the chest/abdomen/pelvis was the most valuable diagnostic tool.
In their ICL, Frassica et al review current recommendations for evaluation, treatment, and
outcomes of patients with metastatic bone tumors.
Shih et al reviewed 177 patients with skeletal metastases and found that in 30% of the patients,
the primary carcinoma could not be diagnosed. Post-mortem studies identified lung as the most
common site of occult tumor.

35. Q’s..
A 56-year-old female is referred for a second opinion after placement of an
intramedullary nail through a presumed metastatic lesion in her proximal
femur. Final biopsy results from the lesion show a high-grade
chondrosarcoma and staging studies show this to be an isolated site of
disease. What treatment should be recommended?
1. Intramedullary nail removal and radiotherapy to the limb
2. Systemic chemotherapy and keep nail in place to prevent fracture
3. Wide proximal femoral resection and hemiarthroplasty followed by
radiotherapy
4. Wide resection including hip disarticulation
5. Palliative care

36. Q’s..
• PREFERRED RESPONSE 4
• Bone lesions require biopsy prior to treatment as placement of an
intramedullary nail through a tumor contaminates the entire bone. In
the treatment of metastatic lesions with an intramedullary nail,
adjuvant radiotherapy has to be dosed over the entire bone due to
implant contamination of the bone. In the case of chondrosarcoma,
which is chemotherapy and radiotherapy resistant, wide resection will
require some type of resection of the entire bone, meaning either a
hip disarticulation or a total femoral resection - removing all
contaminated tissue.

37. Q’s..
What is the most appropriate treatment for a 65-year-old female with a 100-
pack-year tobacco history who presents with a new painful lytic lesion in her
femoral diaphysis?
1. Antegrade femoral nailing with reamings sent to pathology for analysis
2. Antegrade femoral nailing with adjuvant radiotherapy to the lesion
3. Minimally invasive plating of the femur for stabilization and open
cementation of the lesion
4. Referral to medical oncology for chemo-radiotherapy
5. Lesion biopsy with further treatment based on the results of the biopsy

38. Q’s..
• PREFERRED RESPONSE 5
• New lesions which are not diagnosed by imaging and require surgical
intervention need to have an appropriate biopsy with treatment
dictated by the results of the biopsy. While this patient has a
significant tobacco history, incorrect treatment of this lytic bone
lesion could affect both her overall morbidity and mortality. As an
example, a lytic high-grade chondrosarcoma may look exactly like a
metastatic lesion but requires wide surgical excision, not just
stabilization of an impending pathological fracture. Intramedullary
nailing of a chondrosarcoma would spread the tumor the entire
length of the bone and likely require a major amputation, not a limb
salvage operation.

39. Q’s..
What is the most common cause for an aggressive lytic bone lesion in a
patient above 40-years-old?
1. Multiple myeloma
2. Post radiation sarcoma
3. Metastatic bone disease
4. Paget’s sarcoma
5. Lymphoma

40. Q’s..
• PREFERRED RESPONSE 3
• The following malignant bone tumors occur most frequently in patients 40-80-
years old (in order of decreasing frequency): metastatic bone disease, myeloma,
lymphoma, Paget's sarcoma, and post-radiation sarcoma. The skeleton is a
common site for metastasis from several visceral carcinomas. Think BLTPK for
sources of metastasis: breast, lung, thyroid, prostate, and kidney.
The cited article by Rougraff et al recommends a work-up that includes a history
and physical examination, routine laboratory analysis, plain radiography of the
involved bone and the chest, whole-body bone scan, and computed tomography
of the chest, abdomen, and pelvis. These should all be performed prior to biopsy.
Using this diagnostic strategy they were able to identify the primary site of cancer
in 85% of patients in their study.

41. Q’s..
A 51-year-old female with known metastatic breast cancer presents with acute right thigh pain and
inability to bear weight. A radiograph is shown in Figure A. A biopsy is performed that confirms
metastatic breast cancer. What is the next step in management?
1. Local radiation therapy
2. Intramedullary nailing only
3. Intramedullary nailing
and chemotherapy
4. Intramedullary nailing,
radiation therapy to the tumor site,
and chemotherapy
5. Intramedullary nailing,
radiation therapy to the entire femur,
and chemotherapy

42. Q’s..
• PREFERRED RESPONSE 5
• This patient is presenting with biopsy proven metastatic breast cancer and a pathological fracture.
The treatment in this situation is intramedullary nailing with postoperative radiation therapy to
the entire femur and chemotherapy.
Due to the process of placing the intramedullary nail, the treating surgeon contaminates the
ENTIRE femur with breast cancer. The surrounding area is already contaminated with tumor cells
from the fracture, however. While the intramedullary nail will stabilize the pathological fracture, it
does nothing to control the local progression of breast cancer in this patient's leg. Local
radiotherapy will not only improve the local control of disease but it will palliate the patient's
cancer related pain.
Weber et al review bone metastasis to the femur and propose valuable treatment pearls for
clinical decision making and the biology which prevents cancer bearing bones to heal properly
despite appropriate mechanical stabilization.
Swanson et al review the role of the orthopaedic surgeon in evaluating and treating metastatic
bone disease, paying close attention to the necessity to obtain a tissue diagnosis in the event of
presumed metastatic disease PRIOR to proceeding with any treatment plan.

43. references
• Bone, Metastasis. Apoorva Jayarangaiah1; Pramod Theetha Kariyanna2. NCBI Bookshelf.
A service of the National Library of Medicine, National Institutes of Health. Last
Update: June 11, 2018.
• Orthopaedic oncology, primary and metastatic tumors of the skeletal system. Terrance D.
Peabody, samer attar. Springer international publishing Switzerland, 2014
• Multidisciplinary Approach for Bone Metastasis: A Review. Takahiro Kimura, Department
of Urology, Jikei University School of Medicine, may 2018. Cancers 2018, 10, 156
• The seed and soil hypothesis revisited - the role of tumor-stroma interactions in
metastasis to different organs, Int J Cancer. 2011 Jun 1; 128(11): 2527–2535.
• Metastatic bone disease of the pelvis and extremities : rationalizing orthopaedic
treatment. Kirkinis et.al., ANZ J surg (2016)
• Mechanism of metastasis. Hunter K, Crawford N, Alsarraj J. breast cancer res 2008; 10.
• Acquisition o fmetastatic tissue from patients with bone metastases from breast cancer,
Hilton et al. Breast Cancer Res Treat (2011) 129:761–765

44. Thank you