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Selecting prescribed activity of 131I therapy for pediatric patients
                                                                                                                                                                       Glister, O1, Kulkarni, K1, Van Nostrand D1
                                                                                                                                              Washington Hospital Center, Division of Nuclear Medicine1, MedStar Health Research Institute4


                 Learning Objectives                                                                                                ATA Definitions                                                                                                           Iodine 131I Pediatric Dosing Algorithm                                                                                                                                                                                   Conclusion
 1) To review the definition and objectives for 131I remnant                                                                                                                                                                                                                                                                                                                                                                                    After a thorough literature review , there was no definitive
                                                                                                      1) Remnant ablation - Ablation of the small amount of residual
 ablation, adjuvant treatment and treatment of distant                                                                                                                                                                                                                                                                                                                                                                                          recommendation for the use of 131I treatment of differentiated
                                                                                                      normal thyroid remaining after total thyroidectomy may facilitate the
 metastases as defined by the guidelines published by the                                                                                                                                                                                                                                                                                                                                                                                       thyroid carcinoma in the pediatric population. We propose a
                                                                                                      early detection of recurrence based on serum Tg measurement
 American Thyroid Association,                                                                                                                                                                                                                                                                                                                                                                                                                  model decision tree ,as demonstrated to the left, for the
                                                                                                      and=or RAI WBS.(to facilitate detection of recurrent disease and
 2) To review the literature regarding approaches to the                                                                                                                                                                                                                                                                                                                                                                                        management of this population based upon our own practices
                                                                                                      initial staging).
 selection of prescribed activity of 131I for pediatric patients,                                                                                                                                                                                                                                                                                                                                                                               at Medstar Washington Hospital Center.
                                                                                                      2) Adjuvant therapy - to decrease risk of recurrence and disease
 3) To describe the relevant approaches to the selection of                                                                                                                                                                                                                                                                                                                                                                                                                *
                                                                                                      specific mortality by destroying suspected, but unproven metastatic
 pediatric prescribed activity of 131I for the categories of remnant                                  Disease mortality by destroying suspected, but unproven metastatic
 ablation, adjuvant treatment and treatment of metastatic, and                                        disease.
 4) To describe a proposed algorithm for the selection of                                             3) RAI therapy - to treat known persistent disease.                                                                                                             Spreadsheet of Articles Reviewed
 prescribed activity of 131I for pediatric patients.
                                                                                                                                                                                                                                                                                                                                                      Presence of
                                                                                                      Author                                    Title                                           Reference Jrnl                Year   No. of cases      Age in years                           Prescribed Activity of I-131                                                  Histopathology                 Dominant Size (cm)           Differentiation                                                   COMMENTS / SUMMARY
                                                                                                                                                                                                                                                                                                                                                         Mets
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Noted was 6/72 in study died of DTC.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Follow up was for 13 years on average.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             42% developed lung mets, 24% had neck relapses.
                                                                                                M. Schlumberger et Differentiated Thyroid Carcinoma in Childhood: Long Term           Journal of Clinical Endocrinology and                                                                                                                         58% Female, 42%
                                                                                                                                                                                                                              1987         72              < 21       I-131 Dose 1 mCi/kg, 1 mCi/ Kg post-op dose                                                       PTC and FTC, 1 unknown                   5-65 mm               Well differentiated   18% lung mets, 74% palpable nodes; 90% LN involvement.

                             Abstract
                                                                                                al.                Follow-Up of 72 Patients                                                        Metabolism                                                                                                                                            Male
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Relapse of DTC occurred 5 times as often in patients who did not undergo surgery, relapse can occur even after
                                                                                                                                                                                                                                                                                                                                                                                                                                                             complete remission, need lifelong follow up.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Recommended adaptation of surgery to spread of disease.

                                                                                                                                                                                                                                                                                                                                                                                                                                                             Extent of thyroidectomy supported is near total thyroidectomy.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Use in conjunction with lymph node dissection of the neck and I-131 therapy of microscopic regional and distant
                                                                                                                   Differentiated Thyroid Carcinoma (DTC) in Children and                                                                                             1936-1970 (average dose _131 was 21mCi), 1971-1990 (average dose was
                                                                                                J. Harness                                                                                  World Journal of Surgery          1992         89              <18                                                                                           88%                 PTC and FTC                           N/A                 Well differentiated   mets.
                                                                                                                   Adolescents                                                                                                                                        147 mCi), total series average dose 180 mCi I-131.
The guidelines published by American Thyroid Association defines                                                                                                                                                                                                                                                                                                                                                                                             Prior to 1971 50% patients had received head and neck external irradiation.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Decrease in patient disease load afterward correlated with decreased radiation exposure.

three   131
              I therapies in adult patients (i.e., remnant ablation, adjuvant                                                                                                                                                                                                                                                                      76% female, 24%
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Independent variables assessed for their influence on disease progression included age, antecedent thyroid
                                                                                                                                                                                                                                                                                                                                                                                                                                                             irradiation, the presence of extrathyroidal extension of the primary tumor into surrounding tissues, primary tumor
                                                                                                                                                                                                                                                                                                                                                   male. (43% I-131                                                                                          size, regional lymph node involvement, presence of distant metastases at diagnosis, the technique of initial thyroid
treatment, and treatment of distant metastases), and the guidelines                                                Differentiated Thyroid Carcinoma in Childhood: Determinants
                                                                                                                                                                                                                                                                                                                                                   primary treatment
                                                                                                                                                                                                                                                                      As high as 300 mCi for Pt with pulmonary mets. No doses of I-131 reported in (18% for thyroid
                                                                                                                                                                                                                                                                                                                                                                                                                                                             surgery, the technique of lymph node dissection, the existence of positive gross or microscopic margins, the use of
                                                                                                                                                                                                                                                                                                                                                                                                                                                             131 I in initial treatment of the thyroid bed, and histopathologic subtype.
                                                                                                K. Newman          of disease progression in patients < 21 years of age at                     Annals of Surgery              1998        329              < 21                                                                                                              PTC and FTC                           N/A                 Well differentiated
                                                                                                                                                                                                                                                                      article.                                                                     bed, 22% thyroid                                                                                          Overall 67% progression-free survival rate determined at 10 years; best in older patients with complete thyroid
                                                                                                                   diagnosis.
make recommendations for the therapeutic prescribed activity of                       131
                                                                                            I                                                                                                                                                                                                                                                       bed and distant
                                                                                                                                                                                                                                                                                                                                                   mets, 3% distant
                                                                                                                                                                                                                                                                                                                                                                                                                                                             resection.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Biologic rather than treatment factors favor young DTC patients survival > 90%.
                                                                                                                                                                                                                                                                                                                                                        mets)                                                                                                The10q and p21 RAS biological factors in PTC, changes in chromosome 3 FTC related, RET proto-oncogenic
depending on the objectives of these three 131I therapies. However, no                                                                                                                                                                                                                                                                                                                                                                                       mutation may lead to cancer as well.

                                                                                                                                                                                                                                                                                                                                                                                                                                                             Confirmed excellent survival in < 21 years of age even though more mets.
guidelines for the selection of         131
                                              I activity in the pediatric populations           Sin-Ming Chow et   Differentiated Thyroid Carcinoma in Childhood and
                                                                                                                                                                                             Pediatric Blood Cancer           2004         60              <21        80-150 mCi s/p surgery. If relapse, 192 + or - 115 mCi redose.
                                                                                                                                                                                                                                                                                                                                                    recorded as pre- Papillary Thyroid Carcinoma and
                                                                                                                                                                                                                                                                                                                                                      pubertal and    Thyroid Carcinoma (PTC and                   >1                  Well differentiated
                                                                                                                                                                                                                                                                                                                                                                                                                                                              RAI decreases recurrence and increases survival.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             10 year cause specific survival (CSS) was 98.3%.
                                                                                                al.                Adolescence-Clinical Course and Role of Radioiodine
                                                                                                                                                                                                                                                                                                                                                       adolescent                  FTC)                                                                      If < 21 years old have more pulmonary mets and LN mets than > 21.
have been established.               Also, the presentation and outcome of                                                                                                                                                                                                                                                                                                                                                                                   More likely recurrence, but better outcome than >21 years old.

                                                                                                                                                                                                                                                                      Page 418 , Van Nostrand Chart describes guidelines for pediatric dosing
pediatric thyroid cancer are different from adult thyroid cancer, and                                                                                                                                                                                                 including empiric, Reynolds criteria, Schlumberger ( 1mCi/KG).
                                                                                                L. Wartofsky       Radioiodine treatment of distant metastasis.                             Thyroid Cancer, Ed. 2nd           2006                                                                                                                   Not applicable               DTC                              N/A                 Well differentiated                                See prescribed activity description and Thyroid Text chart.
                                                                                                                                                                                                                                                                      Frequently in the range of 30-75 mCi depending upon body weight or surface
therefore the goals of        131
                                    I therapy are different, primarily aimed at                                                                                                                                                                                       area.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             DTC more aggressive in pre-pubertal group.

eradicating disease and increase recurrent free survival. This exhibit                                             Differentiated Thyroid Carcinoma in Pediatric Patients:                                                             27 (10 pre-                    30-100 mCi limited to thyroid, invading the neck 150 mCi, mets:
                                                                                                                                                                                                                                                                                                                                                      70% female,                                      1.87 cm pre-pubertal and 1.99
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Lymph node involvement and lung mets.
                                                                                                L. Lazar           Comparison of Presentation and Course between Pre-pubertal                 Journal of Pediatrics           2009   pubertal and 17       <17        175-200 mCi (adjusted weight based adult dose*body wt (kg)/70 kg.                                      PTC and FTC                                               Well differentiated
                                                                                                                                                                                                                                                                                                                                                       30%male                                                   pubertal
                                                                                                                   Children and Adolescents                                                                                             pubertal)                     Adjust dose based also on thyrotropin levels 0.1-0.5 mIU/L.                                                                                                                            Prepubertal outcome similar to pubertal group with aggressive surgery, I-131 and TSH suppression used.
will review the relevant publications regarding selection of           131
                                                                             I activity in
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Positive family hx of DTC more prevalent in pre-pubertal, showed more extrathyroidal extension.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             AHASA data collected on Chernobyl patients after accident with DTC.
pediatric patients such as, modification of the adult prescribed activity                                                                                                                                                                                             I-131 activities of a median of 51.8 MBq/kg (range, 23.9–73.8 MBq/kg); and
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Weight-based method used.
                                                                                                                                                                                                                                                                      residual disease therapy was performed with a median activity of 98.0 MBq/kg
                                                                                                                   I-131 Activities as high as safely administrable (AHASA) for the
based on patient weight and Reynolds’ use of body surface area,                                 F. Verberg         treatment of children and adolescents with advanced
                                                                                                                                                                                      Journal of Clinical Endocrinology and
                                                                                                                                                                                                   Metabolism
                                                                                                                                                                                                                              2011        180              < 20
                                                                                                                                                                                                                                                                      (range, 56.7–164.7 MBq/kg).                                                  58% female, 42%
                                                                                                                                                                                                                                                                                                                                                        male
                                                                                                                                                                                                                                                                                                                                                                             PTC and FTC                           N/A                 Well differentiated   Possible to use 100 MBq/kg for initial and 200 MBq/kg for follow-uo dosing of I-131.
                                                                                                                   differentiated thyroid cancer (DTC)                                                                                                                                                                                                                                                                                                       Radiation absorbed dose to blood (BD) should not > 2 Gy, deduced from whole body retention.
                                                                                                                                                                                                                                                                      Initial ablation dose 50 MBq/kg with no mets; 100 MBq/kg for subsequent
                                                                                                                                                                                                                                                                                                                                                                                                                                                             Conclusion: Dosimetry of I-131 for children with pulmonary mets; advanced DTC in children and adolescents
dosimetry,        and %48 hour whole body retention.               Subsequently, a                                                                                                                                                                                    treatment if residual disease present.
                                                                                                                                                                                                                                                                                                                                                                                                                                                             200MBq/kg = 5.4 mCi/kg Wt.-adjusted AHASA calculated ranges (137-661 MBq for ablation, 210-775 MBq/kg for
                                                                                                                                                                                                                                                                                                                                                                                                                                                             additional treatments after ablation. Goal = BD of 2 Gy.

simplified empiric and dosimetric approach proposed for selection of                                                                                                                                                                 Not applicable,
                                                                                                                                                                                                                                                                      Does not recommend the 2.7 mCi/kg for ablation and 5.4 mCi/kg for follow up                                                                                                            Consider side effects such as: silaloadenitis, xerostomia, secondary primary malignancy.
                                                                                                                   Pediatric Differentiated Thyroid cancer: can the Prescribed        Journal of Clinical Endocrinology and                                           therapy I-131 that Verberg et al. recommends.                                                                                                                                          Need to evaluate risk of secondary primary malignancy development in children.
                                                                                                D. Van Nostrand                                                                                                               2011    comment by                                                                                                     Not applicable           PTC and FTC                          N/A                 Well differentiated
                                                                                                                   Activity of I-131 be Increased?                                                 Metabolism                                                                                                                                                                                                                                                Need to evaluate sensitivity of bone marrow in pediatric population.
prescribed activity will be described.                                                                                                                                                                                                author only
                                                                                                                                                                                                                                                                      Suggested use of Reynold's method, body surface area or dosimetry.                                                                                                                     Dose: don't exceed 65-70% of 48H WBR (Whole body retention.)



                                                                                                                                                                                                                                                                                      Please see handout for complete list of references / QR.

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Pediatric poster

  • 1. Selecting prescribed activity of 131I therapy for pediatric patients Glister, O1, Kulkarni, K1, Van Nostrand D1 Washington Hospital Center, Division of Nuclear Medicine1, MedStar Health Research Institute4 Learning Objectives ATA Definitions Iodine 131I Pediatric Dosing Algorithm Conclusion 1) To review the definition and objectives for 131I remnant After a thorough literature review , there was no definitive 1) Remnant ablation - Ablation of the small amount of residual ablation, adjuvant treatment and treatment of distant recommendation for the use of 131I treatment of differentiated normal thyroid remaining after total thyroidectomy may facilitate the metastases as defined by the guidelines published by the thyroid carcinoma in the pediatric population. We propose a early detection of recurrence based on serum Tg measurement American Thyroid Association, model decision tree ,as demonstrated to the left, for the and=or RAI WBS.(to facilitate detection of recurrent disease and 2) To review the literature regarding approaches to the management of this population based upon our own practices initial staging). selection of prescribed activity of 131I for pediatric patients, at Medstar Washington Hospital Center. 2) Adjuvant therapy - to decrease risk of recurrence and disease 3) To describe the relevant approaches to the selection of * specific mortality by destroying suspected, but unproven metastatic pediatric prescribed activity of 131I for the categories of remnant Disease mortality by destroying suspected, but unproven metastatic ablation, adjuvant treatment and treatment of metastatic, and disease. 4) To describe a proposed algorithm for the selection of 3) RAI therapy - to treat known persistent disease. Spreadsheet of Articles Reviewed prescribed activity of 131I for pediatric patients. Presence of Author Title Reference Jrnl Year No. of cases Age in years Prescribed Activity of I-131 Histopathology Dominant Size (cm) Differentiation COMMENTS / SUMMARY Mets Noted was 6/72 in study died of DTC. Follow up was for 13 years on average. 42% developed lung mets, 24% had neck relapses. M. Schlumberger et Differentiated Thyroid Carcinoma in Childhood: Long Term Journal of Clinical Endocrinology and 58% Female, 42% 1987 72 < 21 I-131 Dose 1 mCi/kg, 1 mCi/ Kg post-op dose PTC and FTC, 1 unknown 5-65 mm Well differentiated 18% lung mets, 74% palpable nodes; 90% LN involvement. Abstract al. Follow-Up of 72 Patients Metabolism Male Relapse of DTC occurred 5 times as often in patients who did not undergo surgery, relapse can occur even after complete remission, need lifelong follow up. Recommended adaptation of surgery to spread of disease. Extent of thyroidectomy supported is near total thyroidectomy. Use in conjunction with lymph node dissection of the neck and I-131 therapy of microscopic regional and distant Differentiated Thyroid Carcinoma (DTC) in Children and 1936-1970 (average dose _131 was 21mCi), 1971-1990 (average dose was J. Harness World Journal of Surgery 1992 89 <18 88% PTC and FTC N/A Well differentiated mets. Adolescents 147 mCi), total series average dose 180 mCi I-131. The guidelines published by American Thyroid Association defines Prior to 1971 50% patients had received head and neck external irradiation. Decrease in patient disease load afterward correlated with decreased radiation exposure. three 131 I therapies in adult patients (i.e., remnant ablation, adjuvant 76% female, 24% Independent variables assessed for their influence on disease progression included age, antecedent thyroid irradiation, the presence of extrathyroidal extension of the primary tumor into surrounding tissues, primary tumor male. (43% I-131 size, regional lymph node involvement, presence of distant metastases at diagnosis, the technique of initial thyroid treatment, and treatment of distant metastases), and the guidelines Differentiated Thyroid Carcinoma in Childhood: Determinants primary treatment As high as 300 mCi for Pt with pulmonary mets. No doses of I-131 reported in (18% for thyroid surgery, the technique of lymph node dissection, the existence of positive gross or microscopic margins, the use of 131 I in initial treatment of the thyroid bed, and histopathologic subtype. K. Newman of disease progression in patients < 21 years of age at Annals of Surgery 1998 329 < 21 PTC and FTC N/A Well differentiated article. bed, 22% thyroid Overall 67% progression-free survival rate determined at 10 years; best in older patients with complete thyroid diagnosis. make recommendations for the therapeutic prescribed activity of 131 I bed and distant mets, 3% distant resection. Biologic rather than treatment factors favor young DTC patients survival > 90%. mets) The10q and p21 RAS biological factors in PTC, changes in chromosome 3 FTC related, RET proto-oncogenic depending on the objectives of these three 131I therapies. However, no mutation may lead to cancer as well. Confirmed excellent survival in < 21 years of age even though more mets. guidelines for the selection of 131 I activity in the pediatric populations Sin-Ming Chow et Differentiated Thyroid Carcinoma in Childhood and Pediatric Blood Cancer 2004 60 <21 80-150 mCi s/p surgery. If relapse, 192 + or - 115 mCi redose. recorded as pre- Papillary Thyroid Carcinoma and pubertal and Thyroid Carcinoma (PTC and >1 Well differentiated RAI decreases recurrence and increases survival. 10 year cause specific survival (CSS) was 98.3%. al. Adolescence-Clinical Course and Role of Radioiodine adolescent FTC) If < 21 years old have more pulmonary mets and LN mets than > 21. have been established. Also, the presentation and outcome of More likely recurrence, but better outcome than >21 years old. Page 418 , Van Nostrand Chart describes guidelines for pediatric dosing pediatric thyroid cancer are different from adult thyroid cancer, and including empiric, Reynolds criteria, Schlumberger ( 1mCi/KG). L. Wartofsky Radioiodine treatment of distant metastasis. Thyroid Cancer, Ed. 2nd 2006 Not applicable DTC N/A Well differentiated See prescribed activity description and Thyroid Text chart. Frequently in the range of 30-75 mCi depending upon body weight or surface therefore the goals of 131 I therapy are different, primarily aimed at area. DTC more aggressive in pre-pubertal group. eradicating disease and increase recurrent free survival. This exhibit Differentiated Thyroid Carcinoma in Pediatric Patients: 27 (10 pre- 30-100 mCi limited to thyroid, invading the neck 150 mCi, mets: 70% female, 1.87 cm pre-pubertal and 1.99 Lymph node involvement and lung mets. L. Lazar Comparison of Presentation and Course between Pre-pubertal Journal of Pediatrics 2009 pubertal and 17 <17 175-200 mCi (adjusted weight based adult dose*body wt (kg)/70 kg. PTC and FTC Well differentiated 30%male pubertal Children and Adolescents pubertal) Adjust dose based also on thyrotropin levels 0.1-0.5 mIU/L. Prepubertal outcome similar to pubertal group with aggressive surgery, I-131 and TSH suppression used. will review the relevant publications regarding selection of 131 I activity in Positive family hx of DTC more prevalent in pre-pubertal, showed more extrathyroidal extension. AHASA data collected on Chernobyl patients after accident with DTC. pediatric patients such as, modification of the adult prescribed activity I-131 activities of a median of 51.8 MBq/kg (range, 23.9–73.8 MBq/kg); and Weight-based method used. residual disease therapy was performed with a median activity of 98.0 MBq/kg I-131 Activities as high as safely administrable (AHASA) for the based on patient weight and Reynolds’ use of body surface area, F. Verberg treatment of children and adolescents with advanced Journal of Clinical Endocrinology and Metabolism 2011 180 < 20 (range, 56.7–164.7 MBq/kg). 58% female, 42% male PTC and FTC N/A Well differentiated Possible to use 100 MBq/kg for initial and 200 MBq/kg for follow-uo dosing of I-131. differentiated thyroid cancer (DTC) Radiation absorbed dose to blood (BD) should not > 2 Gy, deduced from whole body retention. Initial ablation dose 50 MBq/kg with no mets; 100 MBq/kg for subsequent Conclusion: Dosimetry of I-131 for children with pulmonary mets; advanced DTC in children and adolescents dosimetry, and %48 hour whole body retention. Subsequently, a treatment if residual disease present. 200MBq/kg = 5.4 mCi/kg Wt.-adjusted AHASA calculated ranges (137-661 MBq for ablation, 210-775 MBq/kg for additional treatments after ablation. Goal = BD of 2 Gy. simplified empiric and dosimetric approach proposed for selection of Not applicable, Does not recommend the 2.7 mCi/kg for ablation and 5.4 mCi/kg for follow up Consider side effects such as: silaloadenitis, xerostomia, secondary primary malignancy. Pediatric Differentiated Thyroid cancer: can the Prescribed Journal of Clinical Endocrinology and therapy I-131 that Verberg et al. recommends. Need to evaluate risk of secondary primary malignancy development in children. D. Van Nostrand 2011 comment by Not applicable PTC and FTC N/A Well differentiated Activity of I-131 be Increased? Metabolism Need to evaluate sensitivity of bone marrow in pediatric population. prescribed activity will be described. author only Suggested use of Reynold's method, body surface area or dosimetry. Dose: don't exceed 65-70% of 48H WBR (Whole body retention.) Please see handout for complete list of references / QR.