Approach to metastatic bone disease.....

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FairuzKhamzah

Approach to metastatic bone disease

Health & Medicine

Case 1
57yr old lady
left thigh pain
Dx with breast Ca 2yrs ago
Mastectomy + chemo done
How to proceed?

Case 2
75yr old gentleman
DM/Hpt
Slipped and fell
How to proceed?

Outline
• Defination
• Epidemiology
• Common sites
• Pathophysiology
• Types of lesion
• Aims of Rx
• Presentation
• Investigation
• Managements

Definition
• Secondary malignant neoplastic disease of the skeletal system as a
result of metastasis from a primary tumour

Epidemiology
• Aging population = increased incidence of Metastatic bone disease
• Site for mets
• Lung -> Liver -> Bone
• Lytic lesions in patients >40 yrs - MBD should be considered

Common sites
• Breast
• Lung
• Thyroid
• Kidney
• Prostate
• Hematological
• commonest site = spine > proximal femur > humerus

Pathophysiology
• Paget's Seed & Soil theory
• The 'seeds' (tumor cells) require appropriate 'soil' (the bone micro-
environment) to establish skeletal metastasis

Types of lesions
• Osteolytic bone lesions
• Tumor cells secrete PTHrP (PTH related peptide)
• Bone resorption result in release of
• Transforming growth factor-β (TGF- β)
• Insulin-like growth factor-1 (ILGF-1)
• Stimulate tumor cells to multiply and release more PTHrP
• “Vicious cycle”

Types of lesions
• Osteoblastic lesion
• Due to tumor-secreted endothelin 1

Aim
• Diagnose primary
• Decide on skeletal stabalization

Presentation
• Pain
• HyperCa
• Stones, bones, abdominal groans & pshycic moans
• Pathological #

Management
• Multidisciplinary approach
• Treat life threatening conditions first!
• GOALS:
• pain relief
• preserve/restore function
• maximising quality of life

Non - operative Mx
• Non-operative
• Radiotherapy
• Chemotherapy
• Bisphosphonates - Denosumab
• Hormonal therapy

Operative
• Solitary lesion - CURATIVE - Rx as primary sarcoma
• Multiple lesion - PALLIATIVE

$Indications for surgery • pathological fracture • prophylaxis to lesions that are high risk of fracture • survival > 6 weeks$

Risk assessment Vs Prognosis
• Risk assessment
• Harrington’s criteria
• Mirel’s score
• Prognosis
• WITHOUT spine mets : Katagiri score
• WITH spine mets : Tomita score OR Tokuhashi score

$Harringtons • Harrington’s criteria - fix if any of these occur • cortical bone destruction > 50% • lesion > 2.5cm dimension in proximal femur • pathological avulsion fracture of lesser trochanter • persisting stress pain despite irradiation$

$Mirels Score Risk of fracture Treatment 9 and above 33% Fixation 8 15% ? Dilemma 7 and below 5% Irradiation and observation Mirels criteria Score 1 2 3 Site upper limb lower limb peritrochanteric Pain mild moderate functional Lesion blastic mixed lytic Size < 1/3 1/3 to 2/3 > 2/3$

$Take home message • Consider MSD in patients with lytic bonlesions >40yrs 1. Lytic lesion OR fracture 2. Established primary or unknown primary 3. Solitary or Multiple 4. Risk assessment 5. Prognostic scoring$

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Title: Understanding Giant Cell Tumor of Bone: A Comprehensive Overview Introduction: Giant Cell Tumor of Bone (GCTB) is a rare but potentially aggressive bone tumor that primarily affects young adults. While typically benign, it can be locally destructive and lead to significant morbidity if not managed appropriately. This presentation aims to provide a comprehensive understanding of GCTB, including its epidemiology, pathogenesis, clinical presentation, diagnostic modalities, treatment options, and prognosis. Epidemiology: GCTB accounts for approximately 5% of all primary bone tumors, with a peak incidence in the third and fourth decades of life. It shows a slight female predilection and commonly arises in the epiphyseal regions of long bones, particularly around the knee. Pathogenesis: The exact etiology of GCTB remains elusive, but it is thought to arise from mesenchymal stromal cells. Genetic alterations, including mutations in the H3F3A gene, have been implicated in its pathogenesis. Additionally, dysregulation of the RANK/RANKL/OPG pathway plays a crucial role in the development and progression of GCTB. Clinical Presentation: Patients with GCTB typically present with localized bone pain, swelling, and limited range of motion at the affected joint. Pathologic fractures may occur, especially in larger lesions. Rarely, patients may present with systemic symptoms such as fever and weight loss. Diagnostic Modalities: Diagnostic evaluation of GCTB includes imaging studies such as plain radiographs, which often show characteristic lytic lesions with well-defined margins and cortical thinning. Magnetic resonance imaging (MRI) provides detailed soft tissue evaluation and aids in surgical planning. Biopsy remains the gold standard for definitive diagnosis. Treatment Options: The management of GCTB is challenging and requires a multidisciplinary approach. Treatment options include curettage with or without adjuvant therapy (such as adjuvant bone cement, phenol, or cryotherapy), en bloc resection for aggressive or recurrent tumors, and denosumab therapy for unresectable or metastatic disease. Close surveillance is essential due to the risk of local recurrence. Prognosis: The prognosis of GCTB is generally favorable, with a low incidence of metastasis. However, local recurrence rates range from 10% to 50%, depending on the extent of surgical resection and the use of adjuvant therapy. Long-term follow-up is necessary to monitor for recurrence and late complications. Conclusion: In conclusion, Giant Cell Tumor of Bone poses a significant clinical challenge due to its potential for local recurrence and morbidity. Early diagnosis, appropriate staging, and a tailored treatment approach are crucial for optimizing patient outcomes. Continued research into the molecular mechanisms underlying GCTB pathogenesis and the development of targeted therapies are essential for improving treatment strategies and patient prognosis. Giant Cell Tumor of Bone (GCTB)

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Approach to metastatic bone disease.....

1. Case 1 57yr old lady left thigh pain Dx with breast Ca 2yrs ago Mastectomy + chemo done How to proceed?

2. Case 2 75yr old gentleman DM/Hpt Slipped and fell How to proceed?

3. Approach to metastatic bone disease

4. Outline • Defination • Epidemiology • Common sites • Pathophysiology • Types of lesion • Aims of Rx • Presentation • Investigation • Managements

5. Definition • Secondary malignant neoplastic disease of the skeletal system as a result of metastasis from a primary tumour

6. Epidemiology • Aging population = increased incidence of Metastatic bone disease • Site for mets • Lung -> Liver -> Bone • Lytic lesions in patients >40 yrs - MBD should be considered

7. Common sites • Breast • Lung • Thyroid • Kidney • Prostate • Hematological • commonest site = spine > proximal femur > humerus

8. Pathophysiology • Paget's Seed & Soil theory • The 'seeds' (tumor cells) require appropriate 'soil' (the bone micro- environment) to establish skeletal metastasis

10. Types of lesions • Osteolytic bone lesions • Tumor cells secrete PTHrP (PTH related peptide) • Bone resorption result in release of • Transforming growth factor-β (TGF- β) • Insulin-like growth factor-1 (ILGF-1) • Stimulate tumor cells to multiply and release more PTHrP • “Vicious cycle”

11. Types of lesions • Osteoblastic lesion • Due to tumor-secreted endothelin 1

12. Aim • Diagnose primary • Decide on skeletal stabalization

13. Presentation • Pain • HyperCa • Stones, bones, abdominal groans & pshycic moans • Pathological #

14.

15. Management • Multidisciplinary approach • Treat life threatening conditions first! • GOALS: • pain relief • preserve/restore function • maximising quality of life

16. Non - operative Mx • Non-operative • Radiotherapy • Chemotherapy • Bisphosphonates - Denosumab • Hormonal therapy

17. Operative • Solitary lesion - CURATIVE - Rx as primary sarcoma • Multiple lesion - PALLIATIVE

18. Indications for surgery • pathological fracture • prophylaxis to lesions that are high risk of fracture • survival > 6 weeks

19. Risk assessment Vs Prognosis • Risk assessment • Harrington’s criteria • Mirel’s score • Prognosis • WITHOUT spine mets : Katagiri score • WITH spine mets : Tomita score OR Tokuhashi score

20. Harringtons • Harrington’s criteria - fix if any of these occur • cortical bone destruction > 50% • lesion > 2.5cm dimension in proximal femur • pathological avulsion fracture of lesser trochanter • persisting stress pain despite irradiation

21. Mirels Score Risk of fracture Treatment 9 and above 33% Fixation 8 15% ? Dilemma 7 and below 5% Irradiation and observation Mirels criteria Score 1 2 3 Site upper limb lower limb peritrochanteric Pain mild moderate functional Lesion blastic mixed lytic Size < 1/3 1/3 to 2/3 > 2/3

22. Katagiri Scoring - 2014

23. Katagiri score

24. Tokuhashi Scoring

25. Tomita scoring

26.

27. Take home message • Consider MSD in patients with lytic bonlesions >40yrs 1. Lytic lesion OR fracture 2. Established primary or unknown primary 3. Solitary or Multiple 4. Risk assessment 5. Prognostic scoring

28. Case 1 57yr old lady left thigh pain Dx with breast Ca 2yrs ago Mastectomy + chemo done How to proceed?

29. Case 2 75yr old gentleman DM/Hpt Slipped and fell How to proceed?

Editor's Notes

Detachment of tumor cellsInvasion of tumour cells into surrounding tissue to reach vesselsIntravasation into vessels lumenEvasion ( Avoidance) of host defense mechanismAdherence to endothelium at remote locationExtravasation from vessels into surrounding tissueSurvival and growth within the tissueEstablish own blood supply

Approach to metastatic bone disease.....

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Editor's Notes