Questions and Answers
Questions and Answers
Following the formal presentations at this conference, the floor
was thrown open to questions from the audience. Following are
selected questions and answers that were deemed of particular
· Question: If you plan to give a patient a 4 mCi dose of
Sr-89, how do you advise the physicist to prepare the dose?
· Answer: Dr. Porter--Most clinicians use the reference dose
and date recorded on the label to determine the dosage at the
time of administration. However, the NRC regulations listed in
the Federal Register require that any radioisotope dose in excess
of 10 mCi must actually be measured. Although this currently applies
only to gamma-emitters, the NRC has set forth a proposal that
all alpha and beta emitters also require internal measurements,
indicating that proper records must be maintained. This is extremely
important to those of us involved in Sr-89 therapy.
The current definition of misadministration are: The wrong patient,
route, or dose (by greater than 20% of the prescribed dosage).
The problem encountered in Sr-89 calibration is the difficulty
measuring the bremsstrahlung (radiation arising from an interaction
between beta particles and surrounding atomic nuclei) to the beta
radiation, the minor Sr-89 gamma component of 909 KeV (1%), and
the variation in the Sr-85 contamination (gamma component, 514
KeV). In addition, the wall thickness and type of container used
imposes more variability. For example, with a level of Sr-85 contamination
typically between 0.1 and 0.2%, the difference in the calibrated
response can be 27%, exemplifying the importance of accurately
detailed contamination levels from the manufacturer for each batch
Therefore, a new radiopharmaceutical rule was proposed by the
NRC/NIST in October 1993. It states that all alpha- and beta-emitting
radiopharmaceutical dosages must be measured by direct assessment
of activity using a combination of measurements and calculations,
except for unit dosages obtained from a manufacturer or preparer
licensed pursuant to 10 CFR 32.72 or equivalent state requirements.
A recognized preparer of pharmaceuticals can be a hospital or
licensed regional pharmacy. Clearly, assaying dosages will soon
become more complicated.
Durability of Strontium
· Question: What is the durability of strontium for pain
relief and how often can you readminister Sr-89 if pain recurs?
· Answer: Dr. Porter--Several studies have indicated that
the duration of the pain response is approximately three to 4
months. If hematologic parameters are not significantly altered,
the patient can be retreated. In patients who are not hematologically
compromised, I often retreat a second time with 3 or 4 mCi doses
without notable problems. However, I am more hesitant to administer
Sr-89 a third time.
The Problem of Extravasation
· Question: We have treated ten patients with strontium and
one developed signs of extravasation. Have any of you experienced
this problem and should there be instructions or cautions regarding
possible extravasation for this agent?
· Answer: Dr. Porter--I believe it depends on how the strontium
is administered. Did you use a butterfly in the vein? If so, that
could be the problem. Butterfly infusion is not recommended.
· Dr. McGowan--I believe that Sr-89 can be safely administered
subcutaneously without concern about extravasation. Since physiologically
it will be handled as calcium, I would not be concerned about
an Adriamycin-like toxicity.
· Comment from an oncologist in the audience--Our staff consists
of well- trained chemotherapy nurses who follow the usual precautions.
Despite this, one patient who developed edema after treatment
with strontium was treated with heat in the emergency room, worsening
the condition. After 6 or 7 hours, I saw this patient, applied
ice and the edema disappeared in 2 or 3 days. Fortunately, there
was no skin desquamation or ulcer formation.
· Dr. Porter--There is probably less of an extravasant reaction
with Sr-89 than with infusion of cytotoxic chemotherapeutic agents,
due to the dose, the infusion rate, and the fact that the skin
has a high tolerance for radiation. For preventive measures, one
should not infuse with a butterfly in a vein. It is more desirable
to infuse Sr-89 into a running I.V. of saline. This provides a
dilutional effect, avoiding the theoretical risk of a cardiac
incident, since strontium is very similar to calcium (although,
to my knowledge, there have been no cardiac incidents due to Sr-89
therapy). Secondly, this mode of administration insures the patency
of the infusion.
The Use of Centerlines
· Question: Do you have any recommendations on using centerlines,
since strontium is a calcium analog?
· Answer: Dr. Porter--I would be relatively cautious about
using an untested centerline.
· Question: Do Board-certified radiation oncologists have
reason to be concerned over medicolegal liabilities for administering
radioactive agents, as opposed to a Board-certified radiologist?
· Answer: Dr. Porter--I would actually assume the opposite,
since our profession is a patient-treating specialty. Strontium-89
is clearly not a diagnostic tool. It is a therapy, which has to
be integrated with other available therapies and the extent of
disease progression. The training accepted for radiation oncology
by the ACGME (Accreditation Committee for Graduate Medical Education)
expects us to have an understanding of isotopes. In some ways,
this particular point in our training has been abrogated. If radiopharmaceuticals
are to become standard in prostate cancer therapy, it behooves
us to attain and retain such expertise.
Who Administers Iodine?
· Question: Who prescribes and administers radioiodine in
the United States?
· Answer: Dr. McGowan--In our jurisdiction in Canada, it
is almost exclusively administered by the radiation therapist.
· Dr. Stone--At our institution, endocrinologists and nuclear
medicine physicians are involved. It is prescribed by the endocrinologists.
· Comment from the audience--In Australia, a radiation oncologist
is licensed for external beam radiotherapy, radiopharmaceutical
therapy, and the use of seed sources. For a fee, we are licensed
to use all three modalities.
· Dr. Poulter--It is variable in our cities. Sometimes it
is administered by nuclear medicine physicians and sometimes by
radiation oncologists. Proper training is the vital issue with
· Dr. Porter--I agree.
· Dr. Poulter--I would like to make a comment related to
this matter. In my experience, nuclear medicine physicians are
not sufficiently trained to make therapeutic judgements for metastatic
bone disease. They must be made more familiar with alternative
therapy options. The administration of the radiopharmaceutical
is not the only issue. The appropriateness of Sr-89 treatment
must be determined by those with experience in treating metastatic
· Comment from the audience--There are really two factors
that must be considered. There is the licensing to prescribe/order
the radiopharmaceutical and the licensing by the NRC to administer
it. I believe that in the United States, radiation oncologists
cannot administer radioactive substances unless they have 30 hours
of radioimmunoassay experience and a Board license. Is that correct?
· Dr. Porter--No. Each state actually has different criteria
that determine whether a physician is properly credentialed. Some
hospitals even have their own criteria and process. The NRC approves
the license if you were Board- certified in radiation oncology,
nuclear medicine, or radiology before a certain year. In addition,
there is no limitation concerning the radiopharmaceuticals you
are licensed to administer.
However, the NRC apparently requires dose calibration by the clinician
and most dose calibrators do not have Sr-89 settings. The setting
must be established with the first Sr-89 shipment, relying on
the accuracy of the manufacturers calibration. There is currently
no standard or requirements for the physician to take measurements
for a pure beta emitter, but they are forthcoming and we must
develop this expertise.
· Question: Dr. Poulter, are there significant toxicities
associated with hemibody radiotherapy as it is administered today?
· Answer: Dr. Poulter--In the early days, the major lethal
toxicity associated with hemibody radiation was radiation pneumonitis.
To the best of my knowledge, correcting for lung transmission
and limiting the dose to 700 cGy has eliminated that problem.
There were no cases of pneumonitis in the RTOG 8206 study.
In terms of hematologic toxicities, there are decreases in platelets
and white blood cell counts, but this reverses spontaneously without
treatment. I suspect that this effect could actually be ameliorated
by growth factors allowing sequential radiation treatments or
higher doses in fractionated therapy. However, with fractionation,
organs such as the liver and kidney become dose limiting and shielding
must be adopted, making the protocol rather complex.