GIANT CELL TUMOR OF

BONE (GCTB)
M. Abdulla M.D.
Prof. of Clinical Oncology
Kasr Al-Aini School of Medicine
Cairo University Egypt.

SUN Annual Meeting

Amgen Symposium
Le Meridien Cairo Airport
Friday 21/10/2016
 Speaker Disclosures:
Member of Advisory Board, Consultant, and Speaker for:
Amgen, Astellas, Astra Zeneca, Hoffman la Roche, Janssen
Cilag, Merck Serono, Novartis, Mundipharma, MSD, Eli Lilly,
Bayer.
 GCTB: Basic Facts & Figures:
3 5% of all primary bone tumors.
15 20% of benign bone tumors.
Mostly benign with aggressive behavior.
Pulmonary metastases in 3 5% indolent behavior

Benign Pulmonary Implants.
Peak Incidence in 3rd & 4th decades of life.
Slight female predominance.
Origin: epiphysis & adjacent metaphysis of long bone, yet flat
bones can be affected.
Presentation: Pain & Swelling (Long Bones), Deformity &
Limitation of Mobility (Spine & pelvic).
Surgical Resection & Curettage The corner stone
in management
 Normal Bone Physiology:

RANKL

Vit D PTH PGE2

IL1

H+ En
z

Bone Formation Bone Resorption

Rana et al. Hematol Oncol Clin N Am 27 (2013) 12611283 Ca++, Cytokines, NTX
 Normal Bone Physiology:
Estrogen + Osteoblast = Osteoprotegerin.
Osteoprotegerin + RANKL = RANK.
RANK Arrest of Osteoclast Differentiation
Apoptosis NO BONE LOSS.

Females:
Premenopausal Preservation of skeletal integrity.
Postmenopausal & Endocrine Therapy (Breast Cancer) Osteoporosis.

Males:
Androgens Aromatase Estrogen Bone Preservation.
Orchiectomy & ADT Androgens Estrogen Bone Loss.

Boyle WJ, et al. Nature 2003; 423:337-42..

 GCTB: Histopathology:

Round to Oval Mononuclear

Cells

Large Osteoclast Giant Cells:

Multinucleated, up to 50.
From monocytes.
> 50% of cellular content.

Osteoblast Precursor Malignant Stromal Cells ++ RANKL

Expression Recruitment of Osteoclasts.
Salerno M, Avnet S, Alberghini M, et al. Histogenetic characterization of giant cell tumor of bone. Clin
Orthop Relat Res 2008;466(9):208191.
 Treatment of GCTB:
1. Surgical Resection with Wide Margins:
Lowest Recurrence Rates.
Might be Associated with DEFORMITIES.
2. Surgical Curettage with Burring :
Most Effective in Long Bones.
Skull, Spinal & Pelvic Locations Mutilating & Incomplete.
3. Intra-Lesional Curettage:
Functional Preservation.
Higher RECURRENCE Rates.
4. Adjuvant Filling:
Phenol, Zinc Chloride, H2O2 .
Variable recurrence rates.
5. Intensity Modulated Radiation Therapy:
Improves Local Control by 80%.
Risk of Subsequent Development of Sarcoma > 45 Gy.

Vult vS et al. J Bone Joint Surg Br 2006;88(4):5315.

Zhen et al. J Bone Joint Surg Br 2004 Mar;86(2):2126.
Roeder et al. Radiat Oncol 2010;5(1).
 RANK-L Inhibitor:

Fully Human IgG2 Antibody

High Affinity to RANKL No

Interaction with RANK

Disrupt Cycle of Bone Destruction

Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of

bone: an open-label, phase 2 study. Lancet Oncology 2010;11(3):27580.
EMERGING ROLE OF
DENOSUMAB IN THE
MANAGEMENT OF GIANT CELL
TUMOR
M. Abdulla M.D.OF
& W.BONE
(1) Ebeid M.D. (GCTB)
(2)

(1)Department of Clinical Oncology

(2)Department of Orthopedics Kasr
Al-Aini School of Medicine Cairo
University Egypt.

EMSOS 28TH Friday, 1 May 2015

Athens, Greece.
 The Study:
Pilot.
Experience of a Single Private Center with MDT Approach.
Salvage Therapy.
 Patients Profile:
17 patients with tissue & radiologic diagnosis of advanced
and/or metastatic GCTB not amenable for curative local
procedures were included in the study, (2010 till now)
Female Sex = 14 patients (82.4%).
Median Age = 29.5 (St Dev = +/- 12.06) years.
All patients had active local disease (Residual Progressive
and not recurrent).
7 patients had pulmonary metastases at presentation.
Prior Therapy:
Failed Surgical Procedure (Incomplete): 13 patients.
Arterial Chemo-embolization: 8 Patients.
Radical Conformal Radiation Therapy: 2 Patients
 Clinical Features:
1ry Anatomical Location:

Anatomical Location Number of Patients

Dorso-lumber & Sacral Spine 10
Tibia 2
Pelvic Bones 2
Femur 1
Ulna 1
Temporal Bone 1
 Clinical Features:
Symptoms at Presentation:

Symptom Number
Pain 17
Neurological Deficits (Motor & Sensory) 10
Shortness of Breath & Cough 4
 Treatment Received:
All patients (Except One) were treated with Denosumab
120 mg by SC injection every 28 days, except one patient
4 patients had received Zoladronic acid 4 mg infusion for a
maximum of 5 injections; (No access to Denosumab at
scheduled dates). 2 patients had started treatment by
Zoladronic acid, and 2 received Zoladronic acid during
treatment course.
2 patients: Systemic Chemotherapy following documented
progression in the lung deposits.
1 patient: No active treatment PS 4.
 Treatment Outcome:
Number received Denosumab injections per patient: 5 18
injection.
Pain: alleviated in all treated patients following the 2nd (13
patients = 81.3%) and the 3rd injection (3 patients = 18.7%).
Neurological Deficits: All patients showed stable neurological
status except 1 patient with Temporal GCTB showed
improvement of Trigeminal Neuralgia.
Pulmonary Metastatic Disease: (7 Patients)
> 50% Regression in 3 patients, of them one underwent metastatectomy
and proved to be of GCTB origin. Maximum response after 7 - 9 courses
then stable disease.
Disease Progression in 2 patients following initial stability, encountered
after 5 & 6 injections.
Stable disease in 1 patient.
1 patient did not receive active treatment (PS 4) with extensive bilateral
lung deposits.
 Treatment Outcome:
Radiologic Response of Primary Tumor:
15 patients had stable radiologic findings all through the study
period.
1 Patient had progressive disease in distal ulna and resected
successfully and kept free locally thereafter although showed
progression of her pulmonary disease.
Adverse Events: No Denosumab related comorbidity was
reported in treated patients.
2010
2012
2014
 Conclusions:
Denosumab is safe and effective in salvage treatment of
advanced and/or metastatic GCTB.
Denosumab is highly effective in pain alleviation due to
associated bone destruction early in course of treatment.
Although pulmonary metastases is rare in GCTB; yet,
Denosumab had shown significant response rate in the
form of stationary course to significant down-sizing up to
resolution of some of pulmonary lesions particularly those
of small size.
Denosumab represents a successful application in the era
of personalized medicine and targeted therapies.
Thank You