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					Guidelines for the Therapeutic
Administration of Samarium-153
for the Palliative Treatment of
Metastatic Bone Disease




                                                  Prepared by
                                     Radiation Safety Program
                                Department of Human Services
                                           120 Spencer Street
                                          MELBOURNE 3000
                                                  March 2003




 Department of Human Services
Contents

Introduction......................................................................................... 3
Clinician Requirements .......................................................................... 4
   Referring Physician/Specialist................................................................................... 4
   Administering Physician/Specialist ............................................................................ 4

Patient Treatment................................................................................. 5
   Indications ............................................................................................................ 5
   Contraindications ................................................................................................... 5
   Relative Contraindications ....................................................................................... 5
   Adverse Reactions .................................................................................................. 5
   Patient preparation................................................................................................. 6
   Administration ....................................................................................................... 6
   Facilities ............................................................................................................... 6
   Post treatment....................................................................................................... 6
   Precautions Following Death of a Patient.................................................................... 8
   Procedure Documentation........................................................................................ 8

Appendix 1 .......................................................................................... 9
   Patient Information and Instruction........................................................................... 9

Appendix 2 ........................................................................................ 10
   General Patient Instructions After Treatment with Samarium 153................................ 10

Appendix 3 ........................................................................................ 11
   Characteristics of Samarium-153 ............................................................................ 11
   Physical Characteristics ......................................................................................... 11
   Table 1: Principle radiation emission data ................................................................ 11
   Table 2: Physical decay chart ................................................................................. 11
   Radiation Dosimetry ............................................................................................. 11
   Table 3: Radiation Absorbed Doses ......................................................................... 12

Bibliography ...................................................................................... 13
Further Information ............................................................................ 14




                                                                                           Samarium-153 Guidelines           2
Introduction
This document has been prepared by the Radiation Safety Program, Department of Human
Services following consultation with the Radiation Advisory Committee and other medical
specialists in the field. It is has been developed to assist physicians and specialists who are
involved in the treatment of patients with samarium 153. The radiopharmaceutical is produced
in Australia by Australian Radioisotopes under the brand name Quadramet.

The radiopharmaceutical consists of radioactive Samarium-153 and a tetraphosphonate
chelator (EDTMP). It is used for the relief of bone pain predominantly in breast cancer patients
and a small percentage of prostrate cancer patients who have developed painful osteoblastic
skeletal metastases. Due to radiation safety concerns and the potential toxicity of this
treatment it was considered necessary to develop guidelines for the administration of
Samarium 153.

Samarium 153 has an affinity for skeletal tissue and concentrates in areas of enhanced
osteoblastic activity. There is significantly greater accumulation of Samarium 153 in the
osteoblastic metastatic bone lesions than in surrounding normal bone. Clinical studies have
shown that Samarium 153 accumulates with a lesion-to-normal bone ratio of approximately 5.

Samarium 153 is cleared rapidly from plasma following intravenous injection and any
Samarium 153 that is not deposited in bone is excreted via the kidneys into the urine.
Localization of Samarium 153 outside of the skeleton is minimal. Patients with more extensive
metastatic bone lesions will excrete less in their urine as a greater proportion of the Samarium
153 will be localised in the skeleton.

Samarium-153 has a half life of 46.3 hours, emits a 103 keV gamma ray suitable for
scintigraphic imaging and a number of beta particles with an average energy of 233 keV. It
has a maximum range in tissue of 3.0 mm.




                                                                    Samarium-153 Guidelines   3
Clinician Requirements


Referring Physician/Specialist
The physician/specialist referring a patient for treatment with Samarium 153 must have
appropriate qualifications, training and experience in managing patients with breast or prostate
cancer. It is extremely important that Samarium 153 be given in the context of overall patient
management that takes into account the current clinical picture, previous radiotherapy and
alternate treatment options appropriate at that time. A multidisciplinary and consultative
approach must be adopted, and the patient must be properly assessed and followed up after
Samarium 153 has been given.

The referring physician/specialist must be a Radiation Oncologist, Medical Oncologist, Urologist
or Breast Specialist.

Patients should be assessed by a Radiation Oncologist before they undergo treatment with
Samarium 153.

Administering Physician/Specialist
All physicians/specialists who administer Samarium 153 for the therapy of painful bone
metastases must have appropriate qualifications, training and experience in the use of
unsealed radioactive sources for therapy. The required qualifications are:

Criterion 1
Joint Specialist Advisory Committee (JSAC), of the Royal Australasian College of Physicians and
the Royal Australian and New Zealand College of radiologists, recognised specialist
qualifications in Nuclear Medicine or Radiation Oncology; and

Criterion 2
adequate prior training, practical experience and a current licence for the therapeutic use of
unsealed sources. The specialist must also be actively practising the use of unsealed sources
for therapy.
Adequate prior training is defined as approved postgraduate study (by formal coursework
and/or within accredited training programs) in the areas of:
• radiation biology;
• radiation dosimetry;
• radiation safety;
• clinical uses of radioisotopes;
• administration of radioisotopes.

Training in these areas must relate to the therapeutic uses of any unsealed sources.
Adequate practical experience is demonstrated by regular therapeutic treatment of patients
with unsealed sources (eg strontium-89, iodine-131, phosphorus-32) over 2 or more years,
and/or supervised patient evaluation and administration of Samarium 153 to a minimum of
three patients. An adequate understanding of the literature on the use of Samarium 153 is
also required.

If further practical experience is required, the required supervision of Samarium 153
administrations should be undertaken by a physician/specialist licensed to use samarium-153.
Specialists wanting to have Samarium-153 added to their licence must contact the Radiation
Safety Program.



                                                                    Samarium-153 Guidelines   4
Patient Treatment


Indications

•   The indications for patient treatment should directly conform to the Therapeutic Goods
    Administration (TGA) approved product information for the use of Samarium 153 in force at
    the time of patient treatment.
•   Always confirm indications on the product information brochure that accompanies the
    product.
•   The current approved indications for Samarium 153 therapy as indicated in the TGA
    approved Samarium 153 product information are:
       For the relief of bone pain in patients with painful osteoblastic skeletal metastases as
       indicated by a positive bone scan. The presence of bone metastases should be
       confirmed prior to therapy.

Contraindications

•     Patients who have severely compromised bone marrow reserves.
•     Patients who are currently undergoing chemotherapy or external beam radiation therapy.
•     Patients who have known hypersensitivity to EDTMP or similar phosphonate compounds
•     Spinal cord compression.

Relative Contraindications

•   Patients who may be incontinent. There will occasionally be instances where urinary
    incontinence can be overcome by urinary catheterisation, and provided that radiation
    safety issues can be satisfactorily addressed, there is no reason to exclude such a patient
    from possible treatment.
•   The presence of urinary obstruction requiring catherisation. Provided appropriate radiation
    safety precautions are observed for handling of urine, such treatment can be satisfactorily
    undertaken.
•   Patients with conditions that require urgent surgical treatment such as impending
    pathological fracture. The treatment of these conditions should take precedence over
    systemic therapy with Samarium 153
•   Patients who may be candidates for other myelosuppressive therapies, including those
    patients with extensive soft tissue metastases. Since Samarium 153 is myelosuppressive,
    it should be administered with caution in these patients.
•   Patients who have been treated with Samarium 153 less than 8 weeks previously.
    Treatment with Samarium 153 should not be repeated for at least 8 weeks after a previous
    dose and only then when white blood cell and platelet counts have sufficiently recovered.
•   Patients with renal impairment since the use of Samarium 153 in patients with renal
    impairment has not been studied.

Adverse Reactions

•   It should be recognised that there may be a transient increase in bone pain within 72 hours
    following injection (flare reaction). Appropriate medications for pain relief should therefore
    be made available for control of pain symptoms during this time period. Patients generally
    experience pain relief several weeks after injection of Samarium 153.



                                                                     Samarium-153 Guidelines      5
•   The possibility of an adverse reaction in patients with renal impairment.

Patient preparation

•   Details of treatment must be described to the patient, and details relevant to radiation
    protection explained, including any restrictions (see example in Appendix 2). These
    instructions should be provided to each patient by the medical specialist responsible for the
    treatment, in consultation with an appropriate radiation protection adviser. Informed
    patient consent to the procedure must be obtained after details have been explained.
•   It is recommended that an appropriate radiation protection adviser be aware of all patients
    considered for treatment with samarium-153, and in appropriate circumstances, should be
    directly involved with the patient’s treatment. It is recommended that therapy with
    Samarium 153 should not be undertaken where radiation protection advice is unavailable
    or when radiation protection guidelines cannot be adequately adhered to.

Administration

•   The administering specialist must be present to carry out the clinical direction (and possibly
    the physical direction) during administration of Samarium 153.
•   The dispensed activity must be checked by two persons either licensed with the
    Department of Human Services to use unsealed radioisotopes or registered with the
    Medical Radiation Technologists Board (MRTB) as a nuclear medicine technologist.
•   Secure intravenous access is mandatory, given the consequences of beta-emitter
    extravasation. An intravenous cannula, preferably of a flexible material, must be inserted
    and a free flowing intravenous infusion established before injection of Samarium 153.

Facilities

•   The majority of patients undergoing Samarium 153 therapy would be outpatients.
    However, for inpatients the design of specialised therapy inpatient rooms and the
    procedures involved in use of Samarium 153 must comply with the Australian Standard
    AS2243.4 - 1998 Safety in Laboratories - Ionizing Radiations.
•   Provided that appropriate radiation safety precautions are observed, patients will not
    require a single room following treatment, although each patient should be reviewed on a
    case by case basis.

Post treatment

•   It is recommended that the patient not return home until at least one urinary void has
    occurred. Monitoring of the patient and/or urine should indicate when it would be
    appropriate to discharge the patient. The decision to discharge the patient should be made
    in consultation with an appropriate radiation protection adviser in accordance with
    ARPANSA, RPS No. 4, Recommendations: Discharge of Patients Undergoing Treatment with
    Radioactive Substances.
•   The responsible physician should assess each patient’s requirements and social
    circumstances to determine if the patient can be sent home.
•   The patient must be provided with an information card, which includes their personal
    details, radionuclide administered (i.e. samarium 153), the activity administered, date of
    administration, name and contact number of their doctor and / or radiation protection
    adviser for emergencies or other hospitalisation, duration of radiation safety restrictions
    and any specific advice relevant to the patient’s individual circumstances. This information
    should be provided by the medical specialist responsible for treatment, in consultation with
    an appropriate radiation protection adviser. The patient information card should be carried




                                                                     Samarium-153 Guidelines   6
    on the patient until the date when restrictions cease. This information should also be
    provided to the referring doctor (see Figure 1 in Appendix 1 for example).
•   General radiation protection instructions, relating to things such as personal hygiene and
    laundering should be provided to the patient (see Appendix 2 for example).
•   A separate information card containing date of next blood test appointment or any other
    medical appointments and names and telephone numbers for follow up advice should be
    provided (see Figure 2 Appendix 1 for example). This information is specifically for the
    patient.
•   It should not be necessary for the patient to take special precautions if in contact with
    children or pregnant women when returning home. However international radiation
    protection principals recommend keeping radiation doses as low as reasonably practicable.
    This can be achieved by the patient minimising the time spent in close proximity to children
    and pregnant women for 48 hours following treatment with Samarium 153.
•   Appropriate follow-up of patients should be undertaken, and clearly scheduled prior to
    administration of Samarium 153. Regular monitoring of blood counts to detect possible
    toxicity should be performed following treatment and monitoring of the patient’s symptoms
    should also be documented on a regular basis.
•   The scheduling of blood tests should be left to the discretion of the administering
    physicians/specialist or referring specialist, but should be performed at least at 2-3 week
    intervals until marrow recovery is evident, or 8 weeks have elapsed since treatment.The
    results of these tests should be clearly recorded in the patient’s medical records.

       Suggested check list when planning samarium-153 therapy.
       1    Patient surname.
       2    Referring physician.
       3    Result of bone scan and date of scan.
       4    Result of full blood count, biochemistry screen and date of test.
       5    Relevant details of any previous radionuclide therapy or other bone marrow suppressive
            therapy, especially hemibody radiation therapy.
       6    Notification of Radiation Protection Adviser.
       7    Proposed date of administration.
       8    Patient’s primary language. (An interpreter may need to be present when treatment is
            given.)
       9    Details of where the patient will stay after therapy.
       10   Details of any factors likely to cause radiation protection problems during therapy
            (eg. incontinence, poor mobility).
       11   Arrangements for follow-up blood tests.

•   When administering Samarium 153 to a patient remaining in hospital, careful attention
    should be paid to radiation safety issues, particularly in regard to urine handling and
    disposal (most unbound samarium-153 will be excreted within 6 hours of administration in
    the presence of normal renal function). Radiation protection advice should be obtained
    from an appropriate radiation protection adviser. Provided that appropriate radiation
    safety precautions are observed, patients will not require a single room following
    treatment, although each patient should be reviewed on a case by case basis.
•   When discharging a patient to another institution (eg. nursing home, hospital) details of
    patient therapy (eg residual activity, estimate of activity excreted in the urine) and
    necessary radiation protection procedures must be supplied.




                                                                                 Samarium-153 Guidelines   7
•   The response of the patient to Samarium 153 (pain control, mobility, quality of life, use of
    other medications) should be carefully evaluated and documented. This information will
    allow evaluation of the efficacy of Samarium 153 therapy to be made, and guide further
    treatment (including possible repeat therapy with Samarium 153).

Precautions Following Death of a Patient
Post mortem, cremation and burial aspects, should the patient die with significant
samarium-153 body residue, must be considered.
•   The handling of any corpses containing radioactive materials should be carried out in
    accordance with the requirements of the NHMRC Code of Practice for the Safe handling of
    Corpses Containing Radioactive Materials (1986)
•   Minimising the radiation dose to any person handling the body can be achieved by utilising
    the short half life of samarium-153. By postponing the handling of any corpses for 4 days
    will result in the measured radiation dose being reduced to one quarter.
•   Hospitals are required to ensure that patients and corpses treated with
    radiopharmaceuticals are not released until they are considered safe for handling. On the
    rare occasion that a body containing radiopharmaceuticals is to be cremated and the
    radioactive material has not yet decayed away to an acceptable level, funeral directors,
    cemetery and crematoria staff will be notified by the administering hospital.
•   Written instructions for crematorium staff on the processing of cremation ashes following
    treatment with Samarium 153 can be obtained from the Radiation Safety Program,
    Department of Human Services.

Procedure Documentation
Each centre should have a detailed radiation management plan, which contains written
procedures for the administration of Samarium 153. The following information should also be
included:
•     Contact name/number for the Radiation Protection Adviser in the event of any problems.
•     Procedures for loss or spillage of Samarium 153 (including excreta).
•     Patient follow up arrangements.
•     Nursing care instructions appropriate to the patient’s circumstances.
•     A copy of these guidelines.




                                                                     Samarium-153 Guidelines    8
APPENDIX 1



Patient Information and Instruction

                                             _____________________________
 Patient Name:________________________________
                                                              ____________
 Patient Age:________________________________Patient UR Number:
                                                ___________________________
 Patient Address:________________________________
                                 ________________________________
  ________________________________                              _________
                                              ______________________________
 Referring Specialist for Continuing management
                                       ________________________________
 Contact Number of Referring Specialist:                              ______
                                         ________________________________
 Administering Nuclear Medicine Specialist:                             ___
                                                               ____________
 Date of Therapy Administration:________________________________
                     -                                    __________________
 Activity of Samarium 153: ________________________________
                                                            __________________
 Specific Advice to Patient Based on Individual Circumstances:
                                 ________________________________
  ________________________________                              _________
                                 ________________________________
  ________________________________                              _________
                                 ________________________________
  ________________________________                              _________




Figure 1   Sample Patient Information Card for Samarium 153 Administration


                                            Date of First Appointment:___________________ Doctor: _______________________

                                            Telephone Number for Follow-up Advice During Office Hours: ______________________

                                            (Name of Person to Ask For: ________________________________________________ )

                                            Telephone number for follow-up advice out of normal hours: _______________________

                                            (Name of Person to Ask For: ________________________________________________ )

                                            Name of Person Responsible for Radiation Safety Advice: ________________________

                                            Telephone and Fax Numbers for Follow-up Radiation Safety Advice: ____________

                                            Telephone:_________________________________ Fax: __________________________




Figure 2 Sample Information Card to Give to Patients



                                                                                                          Samarium-153 Guidelines   9
APPENDIX 2



General Patient Instructions After Treatment with Samarium 153
Samarium 153 is a radiopharmaceutical that is used for the treatment of bone pain in patients
with metastatic bone cancer. It is important that you are aware of the general precautions
that you should undertake after receiving this treatment. Your administering specialist and/or
radiation protection adviser will explain any specific precautions to you, and can answer any
questions that you may have.

As your urine may be slightly radioactive after treatment with Samarium 153, you are advised
to take the following precautions:

Personal hygiene and laundering instructions for the first 12 hours after treatment with
Samarium 153

•   Where a normal toilet is available it should be used in preference to a urinal. The sitting
    posture should be used in preference to the standing posture.
•   Wipe up any spilled urine with a tissue and flush it away.
•   Ensure that you always thoroughly wash your hands after using the toilet.
•   Immediately wash any linen or clothes that become stained with urine. Wash them
    separately from other clothes and rinse thoroughly.

Further instructions

•   Please keep your patient information card with you and bring it to the attention of your
    physician/specialist should you require medical care such as an operation or hospital
    admission within the next 2 weeks.
•   Specifically, please bring this notice to the attention of your physician/specialist should you
    develop difficulty with passing urine or incontinence of urine so they may contact the
    appropriate radiation protection adviser for advice on management of potentially
    radioactive urine.
•   Make sure to keep appointments for follow-up blood tests.
•   If possible, it is recommended that you minimise the time spent in close proximity to
    children and pregnant women for 48 hours following treatment with Samarium 153.




                                                                       Samarium-153 Guidelines    10
APPENDIX 3



Characteristics of Samarium-153



Physical Characteristics
Half-life: 46.7 hours
Average beta energy: 233 keV per decay
Average beta particle range in water: 0.5 mm
Specific gamma ray constant: 2.44 × 10-5 mGy/MBq/h at 1 m.
Half value thickness of lead for Sm-153: 0.1 mm
The use of 1 mm of lead will decrease the external radiation exposure by a factor of
approximately 1000.

Table 1: Principle radiation emission data

              Principle Radiation                       Energy (keV)               Abundance
                       Beta                            640 (maximum)                   30%
                       Beta                            710 (maximum)                   50%
                       Beta                            810 (maximum)                   20%
                     Gamma                                  103                        29%


Table 2: Physical decay chart

             Time (hours)*                    Factor              Time (hours)*           Factor
                  -48.0                         2.05                   +1.0                0.99
                  -36.0                         1.71                   +2.0                0.97
                  -24.0                         1.43                   +3.0                0.96
                  -20.0                         1.35                   +4.0                0.94
                  -16.0                         1.27                   +6.0                0.91
                  -12.0                         1.20                   +8.0                0.89
                   -8.0                         1.13                   +12.0               0.84
                   -6.0                         1.09                   +16.0               0.80
                   -4.0                         1.06                   +20.0               0.74
                   -3.0                         1.05                   +24.0               0.70
                   -2.0                         1.03                   +36.0               0.58
                   -1.0                         1.02                   +48.0               0.49

       *Time = hours before (-) or after (+) calibration.


Radiation Dosimetry
The estimated absorbed radiation doses to an average adult patient from an i.v. injection of
Quadrament are shown in Table 3. The dosimetry estimates were based on clinical
biodistribution studies using methods developed for radiation dose calculations by the Medical
Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine.



                                                                                  Samarium-153 Guidelines   11
As Samarium 153 is excreted in the urine, radiation exposure was based on a urinary voiding
interval of 4.8 hours. Radiation dose estimates for bone and marrow assumes that
radioactivity is deposited on bone surfaces, in accordance with autoradiograms of bone
samples taken from patients who received Samarium 153.

The electron emissions from samarium-153 are abundant, with energies up to 810 keV, rapid
blood clearance of Samarium 153 and low energy and abundant photon emissions. This
generally results in low radiation doses to those parts of the body where the complex does not
localise.
When blastic osseous metastases are present, significantly enhanced localisation of the
radiopharmaceutical will occur, with correspondingly higher doses to the metastases compared
with normal bone and other organs.

The recommended dose of Samarium 153 is 37 MBq/kg. The maximum additional effective
dose that may result from the administration of 37 MBq/kg to a 70 kg patient, from the
presence of impurity Europium-154 at the maximum permitted level, is 0.5 mSv/year.




Table 3: Radiation Absorbed Doses
                 Reference: Eary et al, J. Nucl. Med., 1993, 34, 1031-1036.
         Target organ                               mGy/MBq                   mGy/37 MBq
         Bone surfaces                                 6.76                        251
         Red marrow                                    1.54                        57
         Urinary bladder wall                          0.97                        36
         Kidneys                                       0.018                      0.67
         Lower large intestine                         0.010                      0.37
         Ovaries                                      0.0086                      0.32
         Muscle                                       0.0076                      0.28
         Small intestine                              0.0062                      0.23
         Upper large intestine                        0.0054                      0.20
         Testes                                       0.0054                      0.20
         Liver                                        0.0051                      0.19
         Spleen                                       0.0049                      0.18
         Stomach                                      0.0041                      0.15
         Whole body                                    0.011                      0.41
         Effective dose: 11.43 mSv/37 MBq




                                                                              Samarium-153 Guidelines   12
Bibliography
1. Samarium 153 (Quadramet) product brochure, code number: SM3M1, AUST R: 62521.
2. Goeckeler WF Samarium Sm 153 Lexidronam for the palliation of painful bone metastases.
   J ANZ Nuclear Medicine Vol. 29 No. 4 (1998) 69-71.
3. National Health & Medical Research Council, Code of Practice for the Safe Handling of
   Corpses Containing Radioactive Material (1998).
4. Australian Standard, AS2243.4-1998: Safety in Laboratories – Ionising Radiations.
5. Radiation Safety Program, Department of Human Services, Guidelines for the Therapeutic
   Administration of Strontium-89, publication no. 95/0386
6. Department of Human Services, Health (Radiation Safety) Regulations, Statutory Rule No:
   165/1994.
7. Australian Radiation Protection and Nuclear Safety Agency (ARPANSA), Discharge of
   Patients Undergoing Treatment with Radioactive Substances, Radiation Protection Series
   No. 4
8. Radiation Safety Program, Department of Human Services, Information for people handling
   deceased persons containing radiopharmaceuticals




                                                                Samarium-153 Guidelines   13
Further Information
For further information please contact:
Radiation Safety Program
Department of Human Services
Phone: (03) 9637 4167
Facsimile: (03) 9637 4508
http://www.dhs.vic.gov.au/phd/hprot/rsu
Medical Radiation Technologists Board
(03) 9637 4168




                                          Samarium-153 Guidelines   14
       Radiation Safety Program
   Department of Human Services
        Phone: 03 9637 4167
         Fax: 03 9637 4508
Email: radiation.safety@dhs.vic.gov.au

				
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