Personalized Treatment in Thyroid Disorders
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Endocrine, Endocrine, Thyroid Cancer |
| Therapuetic Areas: | Endocrinology, Oncology |
| Healthy: | No |
| Age Range: | 21 - 65 |
| Updated: | 12/13/2018 |
| Start Date: | December 11, 2018 |
| End Date: | December 15, 2020 |
| Contact: | Prasanna Santhanam, MBBS, MD |
| Email: | psantha1@jhmi.edu |
| Phone: | 410-550-6023 |
Personalized Treatment Planning for Radio-iodine Therapy of Thyroid Disease
The Collar Therapy Indicator (CoTI) (A device that is placed in collar around the neck
resembling a turtle neck sweater collar with a wire and recording box) has been shown in a
single small previously published experience to provide data regarding radioiodine exposure
that correlates with conventional methods of measuring I-123 and I-131 uptakes after
diagnostic dose administration and/or therapy for thyroid disorders. We hypothesize that the
device's continuous measurement capability will permit more accurate estimates of radiation
exposure to thyroid tissue than conventionally employed methods assessing fractional uptake
at one or a few time points. It may also provide information about the extent of variability
in the absorbed radiation dose among patients with thyroid cancer and hyperthyroidism. By
providing more complete information about individual patient's exposures, it will facilitate
more accurate estimation of the administered I-131 dose requirements for control of
hyperthyroidism and thyroid remnant ablation while reducing the need for repeated visits to
the clinic for dosimetry measurements. The aims of our project include the following: (1)To
compare quantitative imaging-derived thyroid time activity curve to that obtained using the
CoTI and to determine the extent to which there is variability in radiation dose predicted
using conventional methods to that predicted from measurement of the full Time-Activity Curve
(TAC).(2) Evaluate the uptake and clearance kinetics across the 5 patients in each category
as proof of principle for a potential larger trial to investigate use of this device in
optimizing the administered doses of radioactive iodine to achieve therapeutic goals while
minimizing risks of comorbidities, such a post-radioiodine hypothyroidism in patients with
Graves' disease.(3)Evaluate patient experience, convenience, and discomfort in using the CoTI
device with a survey instrument.
resembling a turtle neck sweater collar with a wire and recording box) has been shown in a
single small previously published experience to provide data regarding radioiodine exposure
that correlates with conventional methods of measuring I-123 and I-131 uptakes after
diagnostic dose administration and/or therapy for thyroid disorders. We hypothesize that the
device's continuous measurement capability will permit more accurate estimates of radiation
exposure to thyroid tissue than conventionally employed methods assessing fractional uptake
at one or a few time points. It may also provide information about the extent of variability
in the absorbed radiation dose among patients with thyroid cancer and hyperthyroidism. By
providing more complete information about individual patient's exposures, it will facilitate
more accurate estimation of the administered I-131 dose requirements for control of
hyperthyroidism and thyroid remnant ablation while reducing the need for repeated visits to
the clinic for dosimetry measurements. The aims of our project include the following: (1)To
compare quantitative imaging-derived thyroid time activity curve to that obtained using the
CoTI and to determine the extent to which there is variability in radiation dose predicted
using conventional methods to that predicted from measurement of the full Time-Activity Curve
(TAC).(2) Evaluate the uptake and clearance kinetics across the 5 patients in each category
as proof of principle for a potential larger trial to investigate use of this device in
optimizing the administered doses of radioactive iodine to achieve therapeutic goals while
minimizing risks of comorbidities, such a post-radioiodine hypothyroidism in patients with
Graves' disease.(3)Evaluate patient experience, convenience, and discomfort in using the CoTI
device with a survey instrument.
Radioiodine treatment for thyroid disorders represented an early example of individualized
medicine. Since its introduction 80 years ago, the therapeutic I-131 dosage has usually been
tailored to individual patient requirements based on the uptake of a tracer radioiodine dose.
Various techniques have been employed to estimate the administered dose of I-131 for optimal
therapeutic benefit. Estimated exposure has typically been extrapolated from the results of
activity measurements at one or two time points, e.g., at 4 and 24 hours. We now know that
treatment of hyperthyroid Graves' disease with these methods lead to a 13-25% rate of failure
to cure hyperthyroidism and a 46-80% rate of long-term hypothyroidism in cured patients.
Similarly, such relatively crude dosimetry doubtless result in significant overtreatment in
the case of remnant ablation for differentiated thyroid cancer.
For patients with differentiated thyroid cancer requiring remnant ablation, the administered
activity has, in most cases, been derived empirically, ranging between 30-100 mci. The high
success rates in ablating remnant thyroid tissue implies that many patients are still treated
with higher 131-I doses than required, with potential side effects, such as radiation
sialadenitis.
Pilot Study Rationale; Our overall objective is to provide the optimal dose to each patient.
This study will apply a novel "wearable" radiation detection technology to determine
continuous cervical measurements over days following tracer radioiodine administration will
provide information that permits the tailoring of subsequent therapeutic radioiodine doses
more precisely to improve clinical outcomes, as described above.
The actual therapeutic dose decisions in this pilot trial, however, will not be based on the
collar device measurements. Patients with Graves' disease will receive 180-200 µCi I-131 per
gram of estimated gland mass based on the conventional method of dose calculation, based on a
24-hour % uptake and gland volume. Most patients with thyroid cancer would receive the 30 mCi
dose for remnant ablation prior to the placement of the COTI device, as per the American
Thyroid Association (ATA) guidelines.
STUDY DESIGN AND METHODS This will be an unmasked prospective pilot study involving patients
with Graves' disease (Group I) and differentiated thyroid cancer (Group II). Five patients in
each group will have radiation activity measurements using the COTI devise. All persons in
the study will receive 131-I treatment based on the current standards of care for dose
estimation.
Study Device; The CoTI has 3 components;
- A collar unit: a gamma detector wrapped around a body part-neck in this case and
contains a scintillating crystal and a silicon photomultiplier. The photon pulse signal
is then converted to digital signals (measuring the counts per second). Usually two
detectors are placed in specified positions.
- A cable that connects the collar unit to the Control Unit
- A control unit that collects the signals and transmits it wirelessly to a hand-held
computer tablet.
Two types of collar devices will be used: the lower activity and the medium activity
1. Lower activity collar for patients with Graves' disease as well as diagnostic I-123 scan
in thyroid cancer patients. These patients typically receive 0.2-1.2 m Ci of
I-123/I-131.
2. Medium activity collar for Patients with thyroid cancer after 131-I ablation, for which
patients typically receive 30-100 mci of I-131.
Study Population;
- Group I: Patients with diffuse toxic goiter (Graves' disease) diagnosed clinically with
no prior history of radioiodine treatment.
- Group II: Patients with differentiated epithelial thyroid cancer who are s/p total
thyroidectomy and candidates for remnant ablation based on ATA guidelines.
IRB approval and HIPPA regulations; Since it is a project involving a medical device which
will be applied to the patients' neck, it will require the following;
1. Institutional Review Board (IRB) regular approval.
2. Registry into ClinicalTrials.gov.
3. Appropriate forms and consent process for the patients. The recruitment of subjects for
the study;
- Informed consent including the benefits and the risks of the Collar device (CoTI)
will be obtained.
- Confidentiality agreement would be signed regarding the CoTI and its application.
- Demographic, clinical and tumor characteristics of the participants will be
obtained, as outlined below.
- The instructions on the application CoTI will be provided in detail.
- Instructions regarding communication in the event of any difficulties will be
provided.
Preparation the patient;
1. The patients will be prepared by general standards of care prior to CoTI placement. For
patients with Graves' disease, any thionamide anti-thyroid meds will be stopped 3-5 days
prior to I-123 diagnostic dose administration. After obtaining written consent, a venous
blood sample will be obtained for work for requisite laboratory evaluation for baseline
labs, as outlined below, and in women, for a pregnancy test. A (low activity) CoTI
device will be placed under supervision and then adjusted for comfort and optimal
activity measurement as a trial and then removed. Background activity of the patient, a
phantom, and the device itself will be measured. After administration of I-123, an
initial uptake at time 0 will be obtained. The CoTI device will then be placed and the
patient will be asked to return to the clinic at scheduled imaging times for Group I.
Anatomical localization of the CoTI in all patients will be standardized by pen
markings.
2. Patients with Graves' disease, who will be administered 200 µCi of I-131 and fitted with
a low-activity CoTI device after administration of the dose. Background activity of the
patient, a phantom and the device itself will be measured prior to placement of the
device. After administration of I-131, an initial uptake at time 0 will be obtained. The
CoTI device will then be placed and the patient will be asked to come back at scheduled
imaging times for Group II. Anatomical localization for the CoTI for all patients will
be standardized by markings.
3. Patients with differentiated thyroid cancer will be placed on a low iodine diet for one
week. Recombinant TSH will be administered on days 1 and 2 (typically Monday and
Tuesday), and the diagnostic I-123 dosage will be administered on day 2. As per the
protocol standard of care, the diagnostic whole-body scan is done on day 3 and the I-131
dose for I-131 ablation (30-100 mci) is administered on day 4.
After obtaining written consent, venous blood sample will be obtained for work for requisite
laboratory evaluation for baseline labs as outlined below, including in women, a pregnancy
test prior to the I-131 remnant ablation dose. The (medium activity) CoTI device will be
placed under supervision and then adjusted for convenience as outlined above. Background
activity of the patient, a phantom, and the device itself will be measured. After
administration of I-131, an initial uptake at time 0 will be obtained. The CoTI device will
then be placed and the patient will be asked to come back at scheduled imaging times for
Group II. Anatomical localization for the CoTI for all patients will be standardized by
markings.
Scheduled Imaging times; Group I - Persons with Graves' Disease
1. After I-123 diagnostic dose - A planar image with a pinhole collimator at time 06.00
hours.
- An uptake only measurement at time 12.00 hours using the uptake probe.
- An uptake only measurement (with the probe) at time 24.00 hours.
- The counts from the handheld device connected to the CoTI would be obtained at
similar times as above with one additional time point of 18.00 hours i.e. 0, 6, 12,
18 and 24 hours.
2. After administration of 200 µCi of I-131 dose
- A first SPECT image would be performed at 6 hours after I-131 dose.
- A Second SPECT image (with a low dose CT for quantification and attenuation
correction) would be performed at 24 hours after I-131 dose.
- A third SPECT image at 48 hours.
- A fourth SPECT image at 72 hours.
- The counts from the handheld device connected to the CoTI would be obtained at
similar times as above with one additional time point of 96.00 hours i.e. 6, 24,
48, 72 and 96.
Group II - Persons with Thyroid Cancer
-A SPECT image would be performed at 24 hours (with low dose CT for quantification and
attenuation correction) after I-131 therapy.
-A second SPECT image at 48 hours.
-A third SPECT image at 72 hours (with low dose CT for quantification and attenuation
correction).
A final SPECT CT image (with low dose CT for quantification and attenuation correction)
at day 7 post therapy.
- The counts from the handheld device connected to the CoTI would be obtained at similar
times as above with one additional time point of 96.00 hours i.e. 24, 48, 96 and day 7.
Data collection, periodic follow up; • Baseline data will include age, gender, BMI;
duration of autoimmune thyroid disease and/or differentiated thyroid cancer,
History/details of thyroid cancer (stage, Fine Needle Aspiration (FNA) findings, final
tumor histopathology, presence of lymph node metastasis thyroglobulin levels- baseline
and stimulated, preoperative ultrasound findings, extent of surgery); presence of
co-morbidities, details of autoimmune thyroid disease (prior anti-thyroid regimen
including duration of discontinuation, thyroid function tests (free thyroxine, free
triiodothyronine, TSH), thyroid antibodies, and thyroid stimulating immunoglobulins ),
duration and history of levothyroxine therapy (in cases with thyroid cancer), results of
neck and thyroid ultrasound, measured neck circumference prior to application of device,
quality of life scores as measured by a questionnaire. Imaging data would be acquired as
outlined above Statistical Analysis; Descriptive data will be outlined for all the
participants tabulating the variables as determined. The intrapatient variability as
well as accuracy and precision of the device will be obtained individually for Group I
and Group II patients. The correlation (non-parametric) Spearman correlation coefficient
will be obtained to assess the relationship between the uptake and findings as obtained
by the collar device and conventional methods of uptake measurement.
medicine. Since its introduction 80 years ago, the therapeutic I-131 dosage has usually been
tailored to individual patient requirements based on the uptake of a tracer radioiodine dose.
Various techniques have been employed to estimate the administered dose of I-131 for optimal
therapeutic benefit. Estimated exposure has typically been extrapolated from the results of
activity measurements at one or two time points, e.g., at 4 and 24 hours. We now know that
treatment of hyperthyroid Graves' disease with these methods lead to a 13-25% rate of failure
to cure hyperthyroidism and a 46-80% rate of long-term hypothyroidism in cured patients.
Similarly, such relatively crude dosimetry doubtless result in significant overtreatment in
the case of remnant ablation for differentiated thyroid cancer.
For patients with differentiated thyroid cancer requiring remnant ablation, the administered
activity has, in most cases, been derived empirically, ranging between 30-100 mci. The high
success rates in ablating remnant thyroid tissue implies that many patients are still treated
with higher 131-I doses than required, with potential side effects, such as radiation
sialadenitis.
Pilot Study Rationale; Our overall objective is to provide the optimal dose to each patient.
This study will apply a novel "wearable" radiation detection technology to determine
continuous cervical measurements over days following tracer radioiodine administration will
provide information that permits the tailoring of subsequent therapeutic radioiodine doses
more precisely to improve clinical outcomes, as described above.
The actual therapeutic dose decisions in this pilot trial, however, will not be based on the
collar device measurements. Patients with Graves' disease will receive 180-200 µCi I-131 per
gram of estimated gland mass based on the conventional method of dose calculation, based on a
24-hour % uptake and gland volume. Most patients with thyroid cancer would receive the 30 mCi
dose for remnant ablation prior to the placement of the COTI device, as per the American
Thyroid Association (ATA) guidelines.
STUDY DESIGN AND METHODS This will be an unmasked prospective pilot study involving patients
with Graves' disease (Group I) and differentiated thyroid cancer (Group II). Five patients in
each group will have radiation activity measurements using the COTI devise. All persons in
the study will receive 131-I treatment based on the current standards of care for dose
estimation.
Study Device; The CoTI has 3 components;
- A collar unit: a gamma detector wrapped around a body part-neck in this case and
contains a scintillating crystal and a silicon photomultiplier. The photon pulse signal
is then converted to digital signals (measuring the counts per second). Usually two
detectors are placed in specified positions.
- A cable that connects the collar unit to the Control Unit
- A control unit that collects the signals and transmits it wirelessly to a hand-held
computer tablet.
Two types of collar devices will be used: the lower activity and the medium activity
1. Lower activity collar for patients with Graves' disease as well as diagnostic I-123 scan
in thyroid cancer patients. These patients typically receive 0.2-1.2 m Ci of
I-123/I-131.
2. Medium activity collar for Patients with thyroid cancer after 131-I ablation, for which
patients typically receive 30-100 mci of I-131.
Study Population;
- Group I: Patients with diffuse toxic goiter (Graves' disease) diagnosed clinically with
no prior history of radioiodine treatment.
- Group II: Patients with differentiated epithelial thyroid cancer who are s/p total
thyroidectomy and candidates for remnant ablation based on ATA guidelines.
IRB approval and HIPPA regulations; Since it is a project involving a medical device which
will be applied to the patients' neck, it will require the following;
1. Institutional Review Board (IRB) regular approval.
2. Registry into ClinicalTrials.gov.
3. Appropriate forms and consent process for the patients. The recruitment of subjects for
the study;
- Informed consent including the benefits and the risks of the Collar device (CoTI)
will be obtained.
- Confidentiality agreement would be signed regarding the CoTI and its application.
- Demographic, clinical and tumor characteristics of the participants will be
obtained, as outlined below.
- The instructions on the application CoTI will be provided in detail.
- Instructions regarding communication in the event of any difficulties will be
provided.
Preparation the patient;
1. The patients will be prepared by general standards of care prior to CoTI placement. For
patients with Graves' disease, any thionamide anti-thyroid meds will be stopped 3-5 days
prior to I-123 diagnostic dose administration. After obtaining written consent, a venous
blood sample will be obtained for work for requisite laboratory evaluation for baseline
labs, as outlined below, and in women, for a pregnancy test. A (low activity) CoTI
device will be placed under supervision and then adjusted for comfort and optimal
activity measurement as a trial and then removed. Background activity of the patient, a
phantom, and the device itself will be measured. After administration of I-123, an
initial uptake at time 0 will be obtained. The CoTI device will then be placed and the
patient will be asked to return to the clinic at scheduled imaging times for Group I.
Anatomical localization of the CoTI in all patients will be standardized by pen
markings.
2. Patients with Graves' disease, who will be administered 200 µCi of I-131 and fitted with
a low-activity CoTI device after administration of the dose. Background activity of the
patient, a phantom and the device itself will be measured prior to placement of the
device. After administration of I-131, an initial uptake at time 0 will be obtained. The
CoTI device will then be placed and the patient will be asked to come back at scheduled
imaging times for Group II. Anatomical localization for the CoTI for all patients will
be standardized by markings.
3. Patients with differentiated thyroid cancer will be placed on a low iodine diet for one
week. Recombinant TSH will be administered on days 1 and 2 (typically Monday and
Tuesday), and the diagnostic I-123 dosage will be administered on day 2. As per the
protocol standard of care, the diagnostic whole-body scan is done on day 3 and the I-131
dose for I-131 ablation (30-100 mci) is administered on day 4.
After obtaining written consent, venous blood sample will be obtained for work for requisite
laboratory evaluation for baseline labs as outlined below, including in women, a pregnancy
test prior to the I-131 remnant ablation dose. The (medium activity) CoTI device will be
placed under supervision and then adjusted for convenience as outlined above. Background
activity of the patient, a phantom, and the device itself will be measured. After
administration of I-131, an initial uptake at time 0 will be obtained. The CoTI device will
then be placed and the patient will be asked to come back at scheduled imaging times for
Group II. Anatomical localization for the CoTI for all patients will be standardized by
markings.
Scheduled Imaging times; Group I - Persons with Graves' Disease
1. After I-123 diagnostic dose - A planar image with a pinhole collimator at time 06.00
hours.
- An uptake only measurement at time 12.00 hours using the uptake probe.
- An uptake only measurement (with the probe) at time 24.00 hours.
- The counts from the handheld device connected to the CoTI would be obtained at
similar times as above with one additional time point of 18.00 hours i.e. 0, 6, 12,
18 and 24 hours.
2. After administration of 200 µCi of I-131 dose
- A first SPECT image would be performed at 6 hours after I-131 dose.
- A Second SPECT image (with a low dose CT for quantification and attenuation
correction) would be performed at 24 hours after I-131 dose.
- A third SPECT image at 48 hours.
- A fourth SPECT image at 72 hours.
- The counts from the handheld device connected to the CoTI would be obtained at
similar times as above with one additional time point of 96.00 hours i.e. 6, 24,
48, 72 and 96.
Group II - Persons with Thyroid Cancer
-A SPECT image would be performed at 24 hours (with low dose CT for quantification and
attenuation correction) after I-131 therapy.
-A second SPECT image at 48 hours.
-A third SPECT image at 72 hours (with low dose CT for quantification and attenuation
correction).
A final SPECT CT image (with low dose CT for quantification and attenuation correction)
at day 7 post therapy.
- The counts from the handheld device connected to the CoTI would be obtained at similar
times as above with one additional time point of 96.00 hours i.e. 24, 48, 96 and day 7.
Data collection, periodic follow up; • Baseline data will include age, gender, BMI;
duration of autoimmune thyroid disease and/or differentiated thyroid cancer,
History/details of thyroid cancer (stage, Fine Needle Aspiration (FNA) findings, final
tumor histopathology, presence of lymph node metastasis thyroglobulin levels- baseline
and stimulated, preoperative ultrasound findings, extent of surgery); presence of
co-morbidities, details of autoimmune thyroid disease (prior anti-thyroid regimen
including duration of discontinuation, thyroid function tests (free thyroxine, free
triiodothyronine, TSH), thyroid antibodies, and thyroid stimulating immunoglobulins ),
duration and history of levothyroxine therapy (in cases with thyroid cancer), results of
neck and thyroid ultrasound, measured neck circumference prior to application of device,
quality of life scores as measured by a questionnaire. Imaging data would be acquired as
outlined above Statistical Analysis; Descriptive data will be outlined for all the
participants tabulating the variables as determined. The intrapatient variability as
well as accuracy and precision of the device will be obtained individually for Group I
and Group II patients. The correlation (non-parametric) Spearman correlation coefficient
will be obtained to assess the relationship between the uptake and findings as obtained
by the collar device and conventional methods of uptake measurement.
Inclusion Criteria:
- Group I
- Patients with Graves' disease confirmed by laboratory testing.
- Patients able to understand English and able to follow instructions. Group II
- Patients with intermediate and high risk differentiated thyroid cancer requiring
radioiodine remnant ablation or moderately high dose I-131 for treatment of
residual cervical disease.
- Persons able to understand simple English and able to follow instructions.
Exclusion Criteria:
- Patients with diseases involving cervical spine, such as spondylosis and severe
degenerative joint disease.
- Pregnant Women, elderly and persons unable to understand simple instructions
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