Musculoskeletal Malignancy: Management

Management of Musculoskeletal Malignancy is a multidisciplinary action that involves surgical, medical, radiological, and oncological teams.

Principle of Management in Musculoskeletal Malignancy

Proper and Detailed Clinical History

Radiological Diagnosis

• X-ray
• CT Chest ( To see for metastasis)
• MRI ( For Local Staging)
• Bone Scan (Skeletal Metastasis)
• PET Scan

Then we reach a clinic-radiological diagnosis of certain Musculoskeletal Malignancy

Histopathological Diagnosis

There are two staging system

1. AJCC Classification
2. Enneking Classification

In this staging system, primary malignant lymphoma and multiple myeloma are not included. Management and Prognosis depend upon staging

Tumor	Chemotherapy	Radiotherapy	Surgery
Osteosarcoma	√	Only palliation (Unresectable sites)	Essential for cure
Ewing Sarcoma	√	– No functional preserving alternatives – If poor responder (+) margin	Usually indicated
Chondrosarcoma	X	X	Essential for cure
Soft tissue Sarcoma	May be	Mostly Yes	Essential for cure

In the rare variant of chondrosarcoma:

1. Mesenchymal chondrosarcoma: Ewing-like chemotherapy
2. Dedifferentiated chondrosarcoma: Osteosarcoma like chemotherapy

Limb Salvage Surgery

It consists of 2 Parts

1. Resection
2. Reconstruction

Absolute Indication:

If limb function is inferior to amputation and external prosthesis we shouldn’t do limb salvage.

Surgical Margin

Intralesional excision: Within the lesion

Marginal excision: Within reach zone: extracapsular

Wide excision: Beyond reach zone + Standard tissue components

Radical: Normal tissue extra compartmental wide margin

How wide?

Still debatable

• 2-3 cm in bone

• At least one healthy muscle margin

• Barriers like physis, periosteum, thick fascia

• Focally close/ marginal/ for neurovascular acceptable

How to reconstruct defects?

1. Endoprosthesis
2. Bone Graft
3. Extracorporeal Radiotherapy (Sterilizing tumor)
   1. Liquid N₂Pasteurization
   1. Microwave technique
4. Rotationoplasty
5. Temporary spacer

Chemotherapy for Osteosarcoma

Methotrexate Based Regime

Adriamycin

High dose methotrexate

Cisplatin

Give Folate and hydrate patient

Non-methotrexate based regime

Adriamycin

Ifosfamide

Cisplatin

Toxicity: Permanent sterilization in the male patient

Doses:

Adriamycin: 25mg/m² intravenous days (1-3) as a continuous 24-hour infusion

Ifosfamide: 1.8g/m² intravenous days (1-5) with mesna

Cisplatinium: 100 mg/m² intravenous days (1-3)

After neoadjuvant Chemotherapy

Excise specimen

The specimen is evaluated for

The margin of surgical resection

Response of chemotherapy is noted based on the percentage necrosis of tumor cells (Huvo’s System)

Grading	Necrosis after chemotherapy
Grade 1	Necrosis
Grade 2	0 – 50 % necrosis
Grade 3	50-99% necrosis
Grade 4	100 % necrosis

Grade  1 and 2 are poor responders and overall survival is decreased and recurrence is increased

Grade 3 and Grade 4 are good responders

Ewing Sarcoma

Neoadjuvant (VIE, VAC):- Local:-Adjuvant (VIE, VAC, VCD)

Vincristine

Cisplatin

Doxorubicin

Etoposide

Picci Grading

Grade	Histological Features
Grade I	Evidence of macroscopic foci of viable tumor cells
Grade II	Only isolated microscopic nodules of viable tumor cells
Grade III	No nodules of viable tumor cells

Prognostic Factors

1. Metastasis: The single most important
   1. Pulmonary
   1. Nodal/ Bony/ Combination ( Worst)
2. Size of the tumor (> 8 cm  is worst)
3. Site: Pelvis/ axial tumor carries a poor prognosis
4. Responders to induction therapy have a good prognosis
5. Complete surgical removal: Wide/ Radical margins

Role of radiotherapy in Musculoskeletal Malignancy:

Limited

Outcome is poor

Indication:

• Positive Margins
• Planned positive surgical margins
• Marginal surgical resection
• The huge volume of disease especially in the pelvis
• Presence of pathological fracture

SKELETAL METASTASIS

Skeletal Metastasis is the third most common metastasis site next to lung and liver

After the age of 40 years, every bone tumor is considered metastatic

70 % of breast and prostatic cancer develop bone metastasis

Approximately, 30-65% of patients with metastatic lung cancer, 47 % of advanced thyroid cancer, and 30% of renal cancer develop bone metastasis.

Pathophysiology:

Willi’s definition: Metastasis is secondary growth originating from detached tumor fragments

Unusual for acral metastasis (distal to elbow and Knees)

Mostly seen in primary in lungs or kidney

Trabecular/ Metaphyseal bone is favored for metastasis

Sluggish flow in hairpin bends provides the chance for tumor cells to migrate in

Clinical Features:

Metastatic lesions commonly present with pain ( on weight bearing and relived on rest): Suggest Impending fractures

Skull lesions may be present with a headache

Vertebral involvement: Presents with girdle pain, numbness, and paresthesia, weakness in the lower and upper limbs with/without loss of bladder and bowel control.

Pathological fractures/ Impending fractures without any known history or treatment for cancers: Commonest scenarios

The proximal femur, Proximal humerus are the commonest sites.

Primary is known: the skeletal lesion is picked up in the workshop or during periodic follow-ups.

Imaging Modalities in metastatic Disease:

Traditionally:- Osteolytic, Osteoblastic or mixed lytic and sclerotic

Osteolytic	Osteoblastic	Mixed
Kidney	BMP	Central clear areas of cortical lysis surrounded by an area of increased density (Sclerosis)
Lungs	Bronchial Carcinoma	Breast
Thyroid	Medulloblastoma	Ovary
Adrenal	Prostate	Cervix
Uterus		Testes
Gastrointestinal
Melanoma

At least 25-75% loss of mineral: before the lesion is visible on X-ray

The extent of destruction on X-ray helps to assess the risk of fracture, the lytic lesion that destroys 50% or more diaphyseal cortex: Can result in a 60-90 % reduction of bone strength: Increase the risk of fracture

Plain X-ray

1989, Mirels: Four Criteria

Mirel’s Criteria:

Points	1	2	3
Location of involved bone	Upper limb	Lower limb	Peri-trochanteric
Pain	Mild	Moderate	Pain aggravated by function
Type of Lesion	Blastic	Mixed	Lytic
Amount of cortical diameter involved	<1/3	1/3-2/3	>2/3

Total maximum score: 12 points

Score <7: No risk of fracture

A score of 9 or more: a 33% risk of fracture

Laboratory diagnosis:

Anemia, thrombocytopenia, thrombocytosis, leucopenia, and eosinophilia

Increase ALP, Increase Serum Calcium

Increase Serum or bone marrow acid phosphate: Prostate Carcinoma

Tumor markers:

Tumor markers	Tumors
ALK gene	Non-small cell lung cancer (NSCLC), Anaplastic large cell lymphomas
Alpha-fetoproteins (AFPs)	Liver cancer and germ cell tumors
B2 microglobulins	CLL, Multiple Myelomas
B-HCG	Choriocarcinomas
BCR-ABL Fusion gene	CML
BRAF mutation V600E	Cutaneous melanoma and colorectal carcinoma
CA 15.3/ CA 27-29	Breast Carcinoma
CA 19-9	Pancreatic, gall bladder, bile duct cancer
CA 125, HE4	Ovarian Cancer
Calcitonin	Medullary thyroid cancer
CEA	Colorectal and breast Cancer
CD 20	Non-Hodgkin lymphoma
Chromogranin A	Neuroendocrine tumors
Cytokeratin 21-1	Lung carcinoma
EG FR	NSCLC
ER PR	Breast Carcinoma
Fibrin, Fibrinogen, Chromosome 3,7,17,9p21	Bladder Carcinoma
HER 2/neu	Breast, Gastric, and Esophageal carcinoma
Immunoglobulin	Multiple myeloma and Walderstrom macroglobulinemia
KIT	GIST, Mucusal melanoma
KRAS mutational analysis	NSCLC, Colorectal
LDH	Germ cell tumor
PSA	Prostate cancer
Thyroglobulin	Thyroid carcinoma

Biopsy

Must prove that the lesion is metastasis

Needle biopsy: Adequate to diagnose 90% of cases.

See also: Limb Salvage Surgery

See also: Radiograph of Bone Tumor