Ακτινοθεραπεία Ξ. ΒακάληςΑκτινοθεραπευτής Ογκολόγος Ιατρικού κέντρου Αθηνών

Disclosures

None

Metastatic Bone DiseaseMetastasis Sites

–Vertebra (69%)–Pelvis (41%)–Femur (25%)–Hip (14%)

Malawer, MM and Delaney, TF. Treatment of Metastatic Cancer to the Bone. In: Devita VT, Hellman S, Rosenberg SA (eds). Cancer: Principles and Practice of Oncology. 4th ed. Philadelphia: JB Lippincott; 1993:2225-2245.

Level of Metastases

Thoracic 70%

Lumbar 20%

Cervical 10%

Radiology: How to Evaluate

Imaging tests– X-ray– Bone scan

Sensitive, not specific. False positives: trauma, arthritis,

infection– CT (“CAT” scan)– PET scan– MRI scan

Bone biopsy – for confirmation

Blood tests– Calcium, alkaline phosphatase

Bone Scan

Bone Scan

A nuclear medicine bone scan would show bone mets as dark areas

PET scans may show the mets very clearly

PET scans can show bone mets that are in hard to see areas like the ribs or scapula

An MRI may show a bone met better than a regular X-ray

MRI imaging

T1 T2

Clinical features of bony metastases

Bone pain Pathological fracture Nerve compression Hypercalcaemia

Life expectancy Biopsy – Histology to predict the

response to non operative management

Stability Clinical presentation – Pain and

Neurological status

APPROACH

Treatment of bone metstasis

Medical. Surgical. Radiotherapy. Radionuclid. Chemotherapy & Hormonal

Therapy

Multi-disciplinary approach

Radiation Therapy

1. Localized irradiation2. Hemibody irradiation

How does RT reduce pain ?

Cell kill – reduced tumor size and pressure effects

Endothelial damage of micro-vasculature – reduced blood flow.

Reduces edema Reduces pain related neuro-transmitter concentrations

Bone – promotes re-mineralisation leading to structural stability.

Indications of Radiotherapy As Primary Treatment

1. Radiosensitive tumor not previously irradiated

2. Widespread spinal metastases with multilevel neural compression

3. Total neurological deficits below the level of compression > 48 hours

4. Patient’s condition (or prognosis) precludes surgery: high surgical risk or short life expectancy

Penas-Prado M, Loghin ME. Spinal cord compression in cancer patients: review of diagnosis and treatment. Curr Oncol Rep. 2008 Jan;10(1):78-85.

Radiotherapy Modalities

Conventional External Beam Radiotherapy (EBRT)

Intensity-modulated radiation therapy (IMRT)

Stereotactic radiotherapy Stereotactic radiosurgery Radioisotopes

Finn MA, Vrionis FD, Schmidt MH. Spinal radiosurgery for metastatic disease of the spine. Cancer Control. 2007 Oct;14(4):405-11.

Radiation Results

•Overall 85% response rate

•Complete relief in 54%

•50% respond by 2 weeks, 80% by 1 month

•Median duration of pain relief 12-15 weeks

•The Xrays or scans may take months to show improvement (Recalcification by 2-3 months)

Bone met at L2

Radiation field

A typical course of radiation is 10 treatments ( in some cases it is necessary to go slower, 20 to 25)

M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical Center

Palliative xrt - bone metastases treatment planning

good margins– e.g. add 1-2 vertebrae on each side

include nearby asymptomatic lesions avoid irradiating entire limb

circumference reduce irradiated volume of

bowel/bladder bone marrow toxicity

Fractionation regimens

8 Gy in 1 fraction 20 Gy in 5 fractions 24 Gy in 6 fractions 30 Gy in 10 fractions

Endpoints using pain relief, narcotic relief and quality of life measures show consistent similarity in the regimens

Single Vs Multi-Fraction

SYSTEMATIC REVIEW

more convenientless costlyshorter time with acute side effects

fear of high doses per fractionhigher retreatment rate( 2-2,5 times higher)concern about toxicity in long-term survivorsflare of bone pain maybe be higher

Single fraction v multifraction

Problematic retreatment Previous treatment to the spine Femoral axial cortical involvment >

3 cm Surgical stabilization procedure Spinal cord compression or

radicular nerve pain

Single fraction v multifraction caution

Re-irradiation

Not covering the spinal cord – 1 x 8 Gy or 5 x 4Gy(Grade C)

Covering the spinal cord – 8 x 2,5 Gy (Grade D)

Adjuvant Radiotherapy

Done after operative decompression

Patchell et al study

Wait 3 weeks for wound healing before starting radiation

Post-operative

Patient received 30Gy/10fx

Radiopharmaceuticals

Use of Radiopharmaceuticals does not obviate the need for EBRT.

Ideal for osteoblastic, multi-focal and wide-spread disease.

Hemi-body Irradiation

For multiple lesions, when facilities for radionuclide therapy is un-available.

More suited for lower hemibody than upper. Ideally treated using 6MV photons or higher Keep lung dose to < 6 Gy for upper HBI

M. Raphael Pfeffer,Oncology Institute, Chaim Sheba Medical

Center

Palliative xrt -single fraction half body iradiation

lower half body 8 Gy upper half body 6 Gy good short term palliation (~3 months) onset of pain relief

– Half Body xrt 50% @ 3 days, 100% @ 14 days

– Focal XRT 50% @ 7 days, 80% @ 14 days Salazar Cancer 1986

Bisphosphonates and RT

“Bisphosphonates and RT can be given concurrently.”

Synergistic effect – Zoledronic acid pauses the cells in G2M phase.

Use of Bisphosphonates does not obviate the need for RT.

– Deliver high doses safely– Possible to irradiate spine without

affecting spinal cord

IMRT, STEREOTACTIC RADIOSURGERY AND STEREOTACTIC RADIOTHERAPY

*De Salles AA, Pedroso AG, Medin P, Agazaryan N, Solberg T,Cabatan-Awang C, et al: Spinal lesions treated with Novalisshaped beam intensity-modulated radiosurgery and stereotacticradiotherapy. J Neurosurg 101 (3 Suppl):435–440, 2004

Metastatic Spinal Cord Compression (MSCC)

Spinal Cord Syndrome

Epidemiology

40% of all cancer patients will develop metastatic spinal disease– 10-20% of these patients will develop spinal

cord compression

White AP, Kwon BK, Lindskog DM, Friedlaender GE, Grauer JN. Metastatic disease of the spine. J Am Acad Orthop Surg. 2006 Oct;14(11):587-98.

Signs & Symptoms

Presents with as:Collapsed vertebral bodySoft tissue mass in the spinal canal

Symptoms Increasing & unexplained pain in neck or

spine Any numbness/ weakness in arms or legs Difficulty in walking and balancing Problems with controlling & emptying bladder

or bowels Any muscle loss or lack of tendon reflex

Location

What happens to the patient in hospital?

– they should start dexamethasone 16mg od if not already on it

– urgent MRI scan of spine– if proven, urgent radiotherapy to cord

compression area

It is an oncologic emergency

Success rates of SCC treatment with Radiotherapy

– depends on level of neurological function at presentation to radiotherapist

– if patient is ambulatory – 70% retain ability to walk

– if patient is paraparetic – 35% retain ability to walk

– if patient is paraplegic – 5% retain ability to walk

Epidural Metastases and Spinal Cord Compression

< 24 hours of immobility - urgent treatment - 300 cGy x 10 fractions; although shorter courses can be used if needed (e.g. 400 cGy x 5) (Grade C).

Established paraplegia > 24 hours – radiotherapy is indicated for pain relief – single dose of 8 Gy (Grade C).

Multidisciplinary Care NOMS1,2

Neurologic Oncologic Mechanical Stability Systemic disease

Systemic Therapy Radiation Therapy Surgery

vs.

1Bilsky MH, Smith M. Surgical approach to epidural spinal cord compression. Hematology/Oncology Clinics of North America.;20(6):1307-1317, 2006

2Bilsky MH, Azeem S. The NOMS framework for decision making in metastatic cervical spine tumors. Current Opinions in Orthopedics 2007;18(3):263-269.

The role of surgery

Indicated if: previous Radio Rx/ no response Radioresistant tumor life expectancy > three months single site unstable spine no tissue diagnosis

RCT comparing surgery followed by RT vs. RT alone

Improvement in surgery + RT– Able to walk: 84% vs 57%– Median time able to walk: 122 vs 13 days– Continent: 156 vs 17 days– Regained ability to walk: (n= 32) 62% vs 19%– Survival: 126 vs 100 days

Patchell, R, Tibbs, PA, Regine, WF, et al. A randomized trial of direct decompressive surgical resection in the treatment of spinal cord compression caused by metastasis (abstract). proc Am Soc Clin Oncol 2003; 22:1.

The role of surgery + RT

A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease

Neuro Oncol 2005 Jan. Klimo et al. Department of Neurosurgery, University of Utah, Salt Lake City, USA

surgery 999 patients: radiation 543 patients

surgical patients were 1.3 times more likely to be ambulatory after treatment and twice as likely to regain ambulatory function

overall ambulatory success rates for surgery and radiation were 85% and 64%

surgery should usually be the primary treatment with radiation given as adjuvant therapy

32% in the group that underwent radiotherapy before surgery

12% in the group of patients first treated by

surgery.

PostOp major wound complications (dehiscence or wound infection)

Portal 8 cm wide Centered on spine Extends one to two vertebral bodies above

and below the epidural metastasis

Radiation field

3D

permits high dose delivery precisely to the target while minimizing exposure to normal tissues

permits high dose delivery precisely to the target

while minimizing exposure to normal tissues

Radiosurgery Recommendations

A strong recommendation can be made with low-quality evidence that radiosurgery should be considered over conventional fractionated radiotherapy for the treatment of solid tumor spine metastases in the setting of oligometastatic disease and/or radioresistant histology in which no relative contraindications exist.

Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: What are the options, indications, and outcomes. Spine 34(22S):S78-92, 2009

Radiosurgery

Results of Radiosurgery

Pain relief in 85 – 100%

Improvement of neurologic symptoms in 75 – 92%

Cyberknife

CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery. 2004 Jul;55(1):89-98;

125 spinal lesions in 115 consecutive patients were treated with a single-fraction radiosurgery technique No acute radiation toxicity or new neurological deficits occurred and Axial and radicular pain improved in 74 of 79 (94%) patients who were symptomatic before treatment.

Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures.Gerszten. Neurosurg Focus 2005 Mar 15;18(3):e8.

CyberKnife radiosurgery underwent single-fraction radiosurgery (at a mean of 12 days after kyphoplasty) in an outpatient setting. Axial pain improved in 24 (92%) of 26 patients during the follow-up period of 7 to 20 months.