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Childhood Thyroid Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
The annual incidence of thyroid cancers is 4.8 to 5.9 cases per 1 million people aged 0 to 19 years, accounting for approximately 1.5% of all cancers in this age group.[1,2] Thyroid cancer incidence is higher in children aged 15 to 19 years (17.6 cases per 1 million people), and it accounts for approximately 8% of cancers arising in this older age group.[1,3] More thyroid carcinomas occur in females than in males.[4] The trend toward larger tumors suggests that diagnostic scrutiny is not the only explanation for the observed results.[5]
Two time-trend studies using the Surveillance, Epidemiology, and End Results (SEER) database have shown a 2% and 3.8% annual increase in the incidence of differentiated thyroid carcinoma in the United States among children, adolescents, and young adults in the 1973 to 2011 and 1984 to 2010 periods, respectively.[1,5] A similar trend towards an increase in the incidence of thyroid cancer among children, adolescents, and young adults over the last two decades has been documented in Canada.[6] A Danish population-based study of thyroid cancer in patients younger than 24 years reported that the age-adjusted incidence rate (per 100,000) increased significantly from 0.36 in 1980 to 0.97 in 2014, with an average annual percent change of 2.9%.[7] No change in overall survival was observed, but a significant increase was seen in the incidence of thyroid cancer among young adults (aged 18–24 years), mainly attributed to an increase among females and patients with papillary carcinoma.
The incidence of thyroid cancer is higher in White people (5.3 cases per 1 million vs. 1.5 cases per 1 million in Black people) and female adolescents (8.1 cases per 1 million vs. 1.7 cases per 1 million in male adolescents).[1]
The papillary subtype is the most common, accounting for approximately 60% of the cases, followed by the papillary follicular variant subtype (20%–25%), the follicular subtype (10%), and the medullary subtype (<10%).The incidence of the papillary subtype and its follicular variant peaks between the ages of 15 and 19 years. The incidence of medullary thyroid cancer is the highest in the age group of 0 to 4 years and declines at older ages (refer to Figure 1).[2]
Figure 1. Incidence of pediatric thyroid carcinoma based on most frequent subtype per 100,000 as a percent of total cohort. Reprinted from International Journal of Pediatric Otorhinolaryngology, Volume 89, Sarah Dermody, Andrew Walls, Earl H. Harley Jr., Pediatric thyroid cancer: An update from the SEER database 2007–2012, Pages 121–126, Copyright (2016), with permission from Elsevier.
Golpanian S, Perez EA, Tashiro J, et al.: Pediatric papillary thyroid carcinoma: outcomes and survival predictors in 2504 surgical patients. Pediatr Surg Int 32 (3): 201-8, 2016.
Dermody S, Walls A, Harley EH: Pediatric thyroid cancer: An update from the SEER database 2007-2012. Int J Pediatr Otorhinolaryngol 89: 121-6, 2016.
Horner MJ, Ries LA, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2006. National Cancer Institute, 2009. Also available online. Last accessed June 03, 2021.
Shapiro NL, Bhattacharyya N: Population-based outcomes for pediatric thyroid carcinoma. Laryngoscope 115 (2): 337-40, 2005.
Vergamini LB, Frazier AL, Abrantes FL, et al.: Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatr 164 (6): 1481-5, 2014.
Pole JD, Zuk AM, Wasserman JD: Diagnostic and Treatment Patterns Among Children, Adolescents, and Young Adults with Thyroid Cancer in Ontario: 1992-2010. Thyroid 27 (8): 1025-1033, 2017.
Schmidt Jensen J, Grønhøj C, Mirian C, et al.: Incidence and Survival of Thyroid Cancer in Children, Adolescents, and Young Adults in Denmark: A Nationwide Study from 1980 to 2014. Thyroid 28 (9): 1128-1133, 2018.
Risk factors for pediatric thyroid cancer include the following:
Radiation exposure. There is an excessive frequency of papillary thyroid adenoma and carcinoma after radiation exposure, either as result of environmental contamination or use of ionizing radiation for diagnosis or treatment.[1,2,3,4] (Refer to the Subsequent Neoplasms section of the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.) The risk increases after exposure to a mean dose of more than 0.05 Gy to 0.1 Gy (50–100 mGy), and follows a linear dose-response pattern up to 30 Gy and then declines, which is greater at younger age of exposure and persists more than 45 years after exposure.[4,5]
Papillary thyroid carcinoma is the most frequent form of thyroid carcinoma diagnosed after radiation exposure.[5] Molecular alterations, including intrachromosomal rearrangements, are frequently found; among them, RET/PTC rearrangements are the most common.[5]
Genetic inheritance. Genetic inheritance plays a role in a subset of thyroid carcinomas. In children, medullary thyroid carcinoma is caused by a dominantly inherited or de novo gain-of-function mutation in the RET proto-oncogene associated with multiple endocrine neoplasia (MEN) type 2, either MEN2A or MEN2B, depending on the specific mutation.[6] When occurring in patients with the MEN syndromes, thyroid cancer may be associated with the development of other types of malignant tumors. (Refer to the PDQ summary on Childhood Multiple Endocrine Neoplasia [MEN] Syndromes Treatment for more information.)
Family history. For thyroid carcinomas of follicular cells, only 5% to 10% are familial cancers. Of those, most familial cases are nonsyndromic, while only a minority occur in the setting of well-defined cancer syndromes with known germline alterations, including the following:[7,8]
APC-associated polyposis.
Carney complex.
PTEN hamartoma tumor syndrome.
Werner syndrome.
DICER1 syndrome.
Cahoon EK, Nadyrov EA, Polyanskaya ON, et al.: Risk of Thyroid Nodules in Residents of Belarus Exposed to Chernobyl Fallout as Children and Adolescents. J Clin Endocrinol Metab 102 (7): 2207-2217, 2017.
Rose J, Wertheim BC, Guerrero MA: Radiation treatment of patients with primary pediatric malignancies: risk of developing thyroid cancer as a secondary malignancy. Am J Surg 204 (6): 881-6; discussion 886-7, 2012.
Lal G, Groff M, Howe JR, et al.: Risk of subsequent primary thyroid cancer after another malignancy: latency trends in a population-based study. Ann Surg Oncol 19 (6): 1887-96, 2012.
Lubin JH, Adams MJ, Shore R, et al.: Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts. J Clin Endocrinol Metab 102 (7): 2575-2583, 2017.
Iglesias ML, Schmidt A, Ghuzlan AA, et al.: Radiation exposure and thyroid cancer: a review. Arch Endocrinol Metab 61 (2): 180-187, 2017 Mar-Apr.
Bauer AJ: Molecular Genetics of Thyroid Cancer in Children and Adolescents. Endocrinol Metab Clin North Am 46 (2): 389-403, 2017.
Acquaviva G, Visani M, Repaci A, et al.: Molecular pathology of thyroid tumours of follicular cells: a review of genetic alterations and their clinicopathological relevance. Histopathology 72 (1): 6-31, 2018.
Francis GL, Waguespack SG, Bauer AJ, et al.: Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 25 (7): 716-59, 2015.
Tumors of the thyroid are classified as adenomas or carcinomas.[1,2,3] Adenomas are benign, well circumscribed and encapsulated nodules that may cause enlargement of all or part of the gland, which extends to both sides of the neck and can be quite large; some tumors may secrete hormones. Transformation to a malignant carcinoma may occur in some cells, which may grow and spread to lymph nodes in the neck or to the lungs. Approximately 20% of thyroid nodules in children are malignant.[1,4]
The following histologies account for the general diagnostic category of carcinoma of the thyroid:
Differentiated thyroid carcinoma: Papillary and follicular carcinoma are often referred to as differentiated thyroid carcinoma. The pathological classification of differentiated thyroid carcinomas in children is based on standard definitions set by the World Health Organization, and the criteria are the same for children and adults. Long-term outcomes for children and adolescents with differentiated thyroid carcinoma are excellent, with 10-year survival rates exceeding 95%.[4,5,6]
Papillary thyroid carcinoma: Papillary thyroid carcinoma accounts for 90% or more of all cases of differentiated thyroid carcinoma occurring during childhood and adolescence. Pediatric papillary thyroid carcinoma may present with a variety of histological variants: classic, solid, follicular, and diffuse sclerosing. Papillary thyroid carcinoma is frequently multifocal and bilateral, and metastasizes to regional lymph nodes in most children. Hematogenous metastases to the lungs occur in up to 25% of cases.[4,7]
Follicular thyroid cancer: Follicular thyroid cancer is uncommon. It is typically a unifocal tumor and more prone to initial hematogenous metastases to lungs and bones. Metastases to regional lymph nodes are uncommon. Histologic variants of follicular thyroid cancer include Hürthle cell (oncocytic), clear cell, and insular (poorly differentiated) carcinoma.[4]
Medullary thyroid carcinoma: Medullary thyroid carcinoma is a rare form of thyroid carcinoma that originates from the calcitonin-secreting parafollicular C cells and accounts for less than 10% of all cases of thyroid carcinoma in children.[6] In children, medullary thyroid carcinoma is usually associated with RET germline mutations in the context of multiple endocrine neoplasia type 2 syndrome.[8]
Anaplastic carcinoma: Less than 1% of pediatric thyroid carcinomas are anaplastic carcinoma.
Dinauer C, Francis GL: Thyroid cancer in children. Endocrinol Metab Clin North Am 36 (3): 779-806, vii, 2007.
Vasko V, Bauer AJ, Tuttle RM, et al.: Papillary and follicular thyroid cancers in children. Endocr Dev 10: 140-72, 2007.
Halac I, Zimmerman D: Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am 34 (3): 725-44, x, 2005.
Sugino K, Nagahama M, Kitagawa W, et al.: Distant Metastasis in Pediatric and Adolescent Differentiated Thyroid Cancer: Clinical Outcomes and Risk Factor Analyses. J Clin Endocrinol Metab 105 (11): , 2020.
Viola D, Romei C, Elisei R: Medullary thyroid carcinoma in children. Endocr Dev 26: 202-13, 2014.
Molecular Features
Thyroid Carcinoma of Follicular Cells
Thyroid tumorigenesis and progression of thyroid carcinomas of follicular cells (differentiated thyroid carcinoma, poorly-differentiated papillary thyroid carcinoma, and anaplastic thyroid carcinoma) are defined by a multistep process that results in aberrant activation of the MAPK and/or PI3K/PTEN/AKT signaling pathways. Comprehensive genomic studies performed over the last decade have defined the landscape of these tumors, as well as their genotype-phenotype correlations. Mutations in BRAF and RAS genes are the most common driver events, followed by gene fusions involving RET or NTRK:[1,2,3]
BRAF: Point mutations of the BRAF gene are the most common alteration found in thyroid carcinoma; the most common mutation is V600E (95% of BRAF-mutated cases). BRAF mutations are found in 40% to 80% of papillary thyroid carcinomas, and in a lower proportion of poorly-differentiated papillary thyroid carcinoma (5%–35%) and anaplastic thyroid carcinoma (10%–50%).[1,3]
The presence of BRAF V600E has been associated with extrathyroidal tumor extension and an increased risk of recurrence; however, its prognostic significance is controversial. BRAF V600E tumors appear to show a broadly immunosuppressive profile with high expression of anti–programmed death-ligand 1 (PD-L1).[1,3]
A retrospective analysis of 80 Brazilian patients younger than 18 years with papillary thyroid carcinoma identified AGK-BRAF fusions and BRAF V600E point mutations.[4]AGK-BRAF fusions, found in 19% of pediatric patients with papillary thyroid carcinoma, were associated with distant metastasis and younger age. BRAF V600E mutations, found in 15% of patients with pediatric papillary thyroid carcinoma, were correlated with older age and larger tumor size.
RAS: Oncogenic RAS activation can occur in any of the RAS family of genes (NRAS, HRAS, and KRAS) although the most frequent alterations are NRAS point mutations. RAS mutations are markers of follicular-patterned thyroid lesions; they are present in 30% to 50% of follicular thyroid carcinoma and in 25% to 45% of follicular variants of papillary thyroid carcinoma, while they are seen in less than 10% of papillary thyroid carcinoma. They are also frequently found in poorly differentiated papillary thyroid carcinoma (20%–50%) and anaplastic thyroid carcinoma (10%–50%) and are believed to promote tumor progression. They have a higher prevalence in areas of iodine deficiency.[1,3]
RET/PTC rearrangements: Multiple RET/PTC rearrangements have been identified in approximately 5% to 25% of papillary thyroid carcinomas and in less than 10% of its follicular variant. They are strongly associated with environmental or therapeutic radiation exposure and are also common among young patients, many of whom present with nodal metastases and aggressive clinicopathological features. [1,3]
NTRK rearrangements: Rearrangements of NTRK1 and NTRK3 have been described in approximately 5% of papillary thyroid carcinomas; however, ETV6-NTRK3 has been reported in 15% of radiation-induced papillary thyroid carcinomas. In young patients and children, NTRK-rearranged papillary thyroid carcinomas may present with lymph node metastases and aggressive clinicopathological features, similar to the presentation of RET-rearranged tumors.[1,3]
DICER1 mutations: Conventional alterations were found in 12 of 30 (40%) papillary thyroid carcinomas (five cases with BRAF V600E, three cases with RET/PTC1, and four cases with RET/PTC3). Pathogenic mutations of DICER1 have been identified in approximately 10% of papillary thyroid carcinomas.[5]
Other alterations include the following:[1,3]
ALK rearrangements have been described in less than 10% of papillary thyroid carcinomas and are commonly associated with dedifferentiation.
Activating mutations of AKT1 have been described in 19% of recurrent or metastatic poorly differentiated papillary thyroid carcinoma.
PPARG rearrangements are present in 20% to 50% of follicular thyroid carcinoma and in a lower proportion of follicular variants of papillary thyroid carcinoma.
TERT-activating mutations are commonly seen in poorly differentiated papillary thyroid carcinoma (20%–50%) and anaplastic thyroid carcinoma (30%–75%), and have also been reported in 10% to 35% of follicular thyroid carcinomas and 5% to 15% of papillary thyroid carcinomas. TERT mutations are believed to promote tumor progression to poorly differentiated papillary thyroid carcinoma and anaplastic thyroid carcinoma and represent a negative prognostic marker.
TP53 is mutated in 40% to 80% of anaplastic thyroid carcinomas and 10% to 35% of poorly differentiated papillary thyroid carcinoma; it is considered to be a final step of tumor progression and a marker for poor prognosis.
The spectrum of somatic genetic alterations seems to be different between pediatric and adult patients when analyzing tumors with similar histologies, as follows:[2,6]
Gene fusions involving RET or, less frequently, NTRK account for approximately 50% of the molecular alterations in pediatric differentiated thyroid carcinoma, compared with approximately 15% in adults.
Gene alterations involving BRAF or RAS, which are present in approximately 70% of thyroid carcinomas diagnosed in adults, are noted in 20% to 40% of pediatric tumors; BRAF mutations have been described in approximately 20% to 30% of cases, while RAS mutations are much less frequently found in pediatrics (5%–10%).
When combining evaluation of DNA and RNA, targetable alterations can be identified in approximately 75% of childhood thyroid carcinomas.
Medullary Thyroid Carcinoma
Medullary thyroid carcinoma is a neuroendocrine malignancy derived from the neural crest-originated parafollicular C cells of the thyroid gland. In children, medullary thyroid carcinoma is a monogenic disorder caused by a dominantly inherited or de novo gain-of-function mutation in the RET oncogene associated with multiple endocrine neoplasia type 2 (MEN2), either MEN2A or MEN2B, depending on the specific mutation. The highest medullary thyroid carcinoma risk is conferred by the RET M918T mutation, which is associated with MEN2B; the RET mutations associated with MEN2A confer a lower medullary thyroid carcinoma risk.[2]
Cancer Genome Atlas Research Network: Integrated genomic characterization of papillary thyroid carcinoma. Cell 159 (3): 676-90, 2014.
Sisdelli L, Cordioli MICV, Vaisman F, et al.: AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma. Pediatr Blood Cancer 66 (7): e27707, 2019.
Wasserman JD, Sabbaghian N, Fahiminiya S, et al.: DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma. J Clin Endocrinol Metab 103 (5): 2009-2015, 2018.
Potter SL, Reuther J, Chandramohan R, et al.: Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma. Pediatr Blood Cancer 68 (1): e28741, 2021.
Clinical Presentation and Prognostic Factors
Differentiated Thyroid Carcinoma
Patients with thyroid cancer usually present with a thyroid mass with or without painless cervical adenopathy.[1] On the basis of medical and family history and clinical constellation, the thyroid cancer may be part of a tumor predisposition syndrome such as multiple endocrine neoplasia (MEN), APC-associated polyposis, PTEN hamartoma tumor syndrome, Carney complex, Werner syndrome, and DICER1 syndrome.[2,3]
Younger age is associated with a more aggressive clinical presentation in differentiated thyroid carcinoma. The following observations have been reported:
In a cross-sectional study involving 20% of community hospitals in the United States, the clinical presentation of 644 pediatric cases was compared with that of more than 43,000 adult cases. Compared with adults, children had a higher proportion of nodal involvement (31.5% in children vs. 14.7% in adults) and lung metastases (5.7% in children vs. 2.2% in adults).[1]
Higher recurrence rates have been associated with younger age at presentation.[4]
Larger tumor size (>1 cm), extrathyroidal extension, and multifocal disease are associated with increased risk of nodal metastases.[5]
When compared with pubertal adolescents, prepubertal children have a more aggressive presentation with a greater degree of extrathyroid extension, lymph node involvement, and lung metastases. However, outcome is similar in the prepubertal and adolescent groups.[6]
In well-differentiated thyroid cancer, male sex, large tumor size, and distant metastases have been found to have prognostic significance for early mortality; however, even patients in the highest risk group who had distant metastases had a 90% survival rate.[7] A French registry analysis found similar outcomes in children and young adults who developed papillary thyroid carcinoma after previous radiation therapy compared with children and young adults who developed spontaneous papillary thyroid carcinoma; patients with previous thyroid irradiation for benign disease, however, presented with more invasive tumors and lymph node involvement.[8]
A review of the National Cancer Database found that patients aged 21 years and younger from lower-income families and those lacking insurance experienced a longer period from diagnosis to treatment of their well-differentiated thyroid cancer and presented with higher-stage disease.[9]
Children with medullary thyroid carcinoma present with a more aggressive clinical course; 50% of the cases have hematogenous metastases at diagnosis.[10] A natural history study of children and young adults with medullary thyroid cancer is being conducted by the National Cancer Institute (NCT01660984). A review of 430 patients aged 0 to 21 years with medullary thyroid cancer reported that older age (16–21 years) at diagnosis, tumor diameter greater than 2 cm, positive margins after total thyroidectomy, and lymph node metastases were associated with a worse prognosis.[11]
From 1997 to 2019, the German Society for Pediatric Oncology and Hematology (GPOH)–Malignant Endocrine Tumors (MET) registry identified a total of 57 patients with medullary thyroid carcinoma and 17 patients with C-cell hyperplasia.[12][Level of evidence: 3iA] In patients with medullary thyroid carcinoma, the median follow-up was 5 years (range, 0–19 years), and the median age at diagnosis was 10 years (range, 0–17 years). The overall survival rate was 87%, and the event-free survival (EFS) rate was 52%. In total, 96.4% of patients were affected by MEN type 2 (MEN2) syndromes; 37 of 42 patients had MEN2A, and 3 of 28 patients had MEN2B (RET M918T mutation). The 10-year EFS rate was 78% for patients with MEN2A and 38% for patients with MEN2B (P < .001). In multivariate analyses, positive lymph node status and postoperatively elevated calcitonin levels were significant adverse prognostic factors for EFS.
In children with hereditary MEN2B, medullary thyroid carcinoma may be detectable within the first year of life and nodal metastases may occur before age 5 years. The recognition of mucosal neuromas, a history of alacrima, constipation (secondary to intestinal ganglioneuromatosis), and marfanoid facial features and body habitus is critical to early recognition and diagnosis because the RET M918T mutation associated with MEN2B is often de novo. Approximately 50% of patients with MEN2B develop a pheochromocytoma, with a varying degree of risk of developing pheochromocytoma and hyperparathyroidism in MEN2A based on the specific RET mutation.[13,14] (Refer to the PDQ summary on Childhood Multiple Endocrine Neoplasia [MEN] Syndromes Treatment for more information.)
For children with de novo RET mutations and no familial history, nonendocrine manifestations, such as intestinal ganglioneuromatosis or skeletal or ocular stigmata, may facilitate early diagnosis and result in better outcomes.[14]
Al-Qurayshi Z, Hauch A, Srivastav S, et al.: A National Perspective of the Risk, Presentation, and Outcomes of Pediatric Thyroid Cancer. JAMA Otolaryngol Head Neck Surg 142 (5): 472-8, 2016.
Ye B, Shi J, Shen C, et al.: Comparison of differentiated thyroid carcinoma recurrence and its clinical features in children of different ages. Oncotarget 8 (29): 48051-48059, 2017.
Kim J, Sun Z, Adam MA, et al.: Predictors of nodal metastasis in pediatric differentiated thyroid cancer. J Pediatr Surg 52 (1): 120-123, 2017.
Lazar L, Lebenthal Y, Steinmetz A, et al.: Differentiated thyroid carcinoma in pediatric patients: comparison of presentation and course between pre-pubertal children and adolescents. J Pediatr 154 (5): 708-14, 2009.
Shayota BJ, Pawar SC, Chamberlain RS: MeSS: A novel prognostic scale specific for pediatric well-differentiated thyroid cancer: a population-based, SEER outcomes study. Surgery 154 (3): 429-35, 2013.
Sassolas G, Hafdi-Nejjari Z, Casagranda L, et al.: Thyroid cancers in children, adolescents, and young adults with and without a history of childhood exposure to therapeutic radiation for other cancers. Thyroid 23 (7): 805-10, 2013.
Garner EF, Maizlin II, Dellinger MB, et al.: Effects of socioeconomic status on children with well-differentiated thyroid cancer. Surgery 162 (3): 662-669, 2017.
Waguespack SG, Rich TA, Perrier ND, et al.: Management of medullary thyroid carcinoma and MEN2 syndromes in childhood. Nat Rev Endocrinol 7 (10): 596-607, 2011.
Raval MV, Sturgeon C, Bentrem DJ, et al.: Influence of lymph node metastases on survival in pediatric medullary thyroid cancer. J Pediatr Surg 45 (10): 1947-54, 2010.
Kuhlen M, Frühwald MC, Dunstheimer DPA, et al.: Revisiting the genotype-phenotype correlation in children with medullary thyroid carcinoma: A report from the GPOH-MET registry. Pediatr Blood Cancer 67 (4): e28171, 2020.
Wells SA, Asa SL, Dralle H, et al.: Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25 (6): 567-610, 2015.
Initial evaluation of a child or adolescent with a thyroid nodule includes the following:
Ultrasound of the thyroid.
Serum thyroid-stimulating hormone (TSH) level.
Serum thyroglobulin level.
Tests of thyroid function are usually normal, but thyroglobulin can be elevated.
Fine-needle aspiration as an initial diagnostic approach is sensitive and useful. However, in doubtful cases, open biopsy or resection should be considered.[1]
Special Considerations for the Treatment of Children With Cancer
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[1] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
Primary care physicians.
Pediatric surgeons.
Radiation oncologists.
Pediatric medical oncologists/hematologists.
Pediatric nurse specialists.
Social workers.
Child-life professionals.
Psychologists.
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[4] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[5,6] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
The Italian Tumori Rari in Eta Pediatrica group defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.[7]
The Children's Oncology Group has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.).[8] These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.[9]
Most cancers within subgroup XI are either melanomas or thyroid cancer, with other types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer such as the PDQ summary on Thyroid Cancer Treatment (Adult).
Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed August 18, 2021.
Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.
Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.
DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.
Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.
Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. National Cancer Institute, 2015. Also available online. Last accessed June 22, 2021.
Treatment of Papillary and Follicular Thyroid Carcinoma
Treatment options for papillary and follicular (differentiated) thyroid carcinoma include the following:
Surgery.
Radioactive iodine ablation.
Targeted therapy.
In 2015, the American Thyroid Association (ATA) Task Force on Pediatric Thyroid Cancer published guidelines for the management of thyroid nodules and differentiated thyroid cancer in children and adolescents. These guidelines (summarized below) are based on scientific evidence and expert panel opinion, with a careful assessment of the level of evidence.[1]
Preoperative evaluation.[1]
A comprehensive ultrasound of all regions of the neck using a high-resolution probe and Doppler technique should be obtained by an experienced ultrasonographer. A complete ultrasound examination should be performed before surgery.
The addition of cross-sectional imaging (contrast-enhanced computed tomography [CT] or magnetic resonance imaging) should be considered when there is concern about invasion of the aerodigestive tract. Importantly, if iodinated contrast agents are used, further evaluation and treatment with radioactive iodine may need to be delayed for 2 to 3 months until total body iodine burden decreases.
Chest imaging (x-ray or CT) may be considered for patients with substantial cervical lymph node disease.
Thyroid nuclear scintigraphy should be pursued only if the patient presents with a suppressed thyroid-stimulating hormone (TSH).
The routine use of bone scan or fluorine F 18-fludeoxyglucose positron emission tomography (PET) is not recommended.
Surgery.[1]
Pediatric thyroid surgery is ideally completed by a surgeon who has experience performing endocrine procedures in children and in a hospital with the full spectrum of pediatric specialty care.
Thyroidectomy:
For patients with papillary or follicular carcinoma, total thyroidectomy is the recommended treatment of choice. The ATA expert panel recommendation is based on data showing an increased incidence of bilateral (30%) and multifocal (65%) disease.
In patients with a small unilateral tumor confined to the gland, a near-total thyroidectomy—whereby a small amount of thyroid tissue (<1%–2%) is left in place at the entry point of the recurrent laryngeal nerve or superior parathyroid glands—might be considered to decrease permanent damage to those structures.[2]
Total thyroidectomy also optimizes the use of radioactive iodine for imaging and treatment.
Central neck dissection:
A therapeutic central neck lymph node dissection should be done in the presence of clinical evidence of central or lateral neck metastases.[3]
For patients without clinical evidence of gross extrathyroidal invasion or locoregional metastasis, a prophylactic central neck dissection may be considered on the basis of tumor focality and size of the primary tumor. However, because of the increased morbidity associated with central lymph node dissection, it is important to carefully individualize each case on the basis of the risks and benefits of the extent of dissection.[4]
Lateral neck dissection:
Cytological confirmation of metastatic disease to lymph nodes in the lateral neck is recommended before surgery.
Routine prophylactic lateral neck dissection is not recommended.
Classification and risk assignment.[1]
Despite the limited data in pediatrics, the ATA Task Force recommends the use of the tumor-node-metastasis (TNM) classification system to categorize patients into one of three risk groups. (Refer to the Stage Information for Thyroid Cancer section in the PDQ summary on Thyroid Cancer Treatment [Adult] for more information about the TNM system.) This categorization strategy is meant to define the risk of persistent cervical disease and help determine which patients should undergo postoperative staging for the presence of distant metastasis.
ATA Pediatric Low Risk: Disease confined to the thyroid with N0 or NX disease or patients with incidental N1a (microscopic metastasis to a small number of central neck nodes). These patients are at lowest risk of distant disease but may still be at risk of residual cervical disease, especially if the initial surgery did not include central neck dissection.
ATA Pediatric Intermediate Risk: Extensive N1a or minimal N1b disease. These patients are at low risk of distant metastasis but are at an increased risk of incomplete lymph node resection and persistent cervical disease.
ATA Pediatric High Risk: Regionally extensive disease (N1b) or locally invasive disease (T4), with or without distant metastasis. Patients in this group are at the highest risk of incomplete resection, persistent disease, and distant metastasis.
Postoperative staging and long-term surveillance.[1]
Initial staging should be performed within 12 weeks after surgery; the purpose is to assess for evidence of persistent locoregional disease and to identify patients who are likely to benefit from additional therapy with iodine I 131 (131I). The ATA Pediatric Risk Level (as defined above) helps determine the extent of postoperative testing.
ATA Pediatric Low Risk:
Initial postoperative staging includes a TSH-suppressed thyroglobulin. A diagnostic iodine I 123 (123I) scan is not required.
TSH suppression should be targeted to serum levels of 0.5 to 1.0 mIU/L.
In patients with no evidence of disease, surveillance should include ultrasound at 6 months postoperatively and then annually for 5 years; and thyroglobulin levels (on hormone replacement therapy) every 3 to 6 months for 2 years and then annually.
ATA Pediatric Intermediate Risk:
Initial postoperative staging includes a TSH-stimulated thyroglobulin and diagnostic 123I whole-body scan for further stratification and determination with 131I.
In patients with no evidence of disease, surveillance should include ultrasound at 6 months postoperatively and then every 6 to 12 months for 5 years (and then less frequently); and thyroglobulin levels (on hormone replacement therapy) every 3 to 6 months for 3 years and then annually.
TSH-stimulated thyroglobulin and diagnostic 123I scan should be considered in 1 to 2 years for patients treated with 131I.
ATA Pediatric High Risk:
TSH suppression should be targeted to serum levels of less than 0.1 mIU/L.
TSH-stimulated thyroglobulin and, possibly, a diagnostic 123I scan in 1 to 2 years in patients treated with 131I.
For patients with antithyroglobulin antibodies, consideration can be given to deferred postoperative staging to allow time for antibody clearance, except in patients with T4 or M1 disease.
Radioactive iodine ablation.[1]
The goal of 131I therapy is to decrease the risks of recurrence and to decrease mortality by eliminating iodine-avid disease.
The ATA Task Force recommends the use of 131I for the treatment of iodine-avid persistent locoregional or nodal disease that cannot be resected and known or presumed iodine-avid distant metastases. For patients with persistent disease after administration of 131I, the decision to pursue additional 131I therapy should be individualized on the basis of clinical data and previous response.
To facilitate 131I uptake by residual iodine-avid disease, the TSH level should be above 30 mIU/L. This level can be achieved by withdrawing levothyroxine for at least 14 days. In patients who cannot mount an adequate TSH response or cannot tolerate profound hypothyroidism, recombinant human TSH may be used.
Therapeutic 131I administration is commonly based on either empiric dosing or whole-body dosimetry. Based on the lack of data comparing empiric treatment and treatment informed by dosimetry, the ATA Task Force was unable to recommend one specific approach. However, because of the differences in body size and iodine clearance in children compared with adults, it is recommended that all activities of 131I should be calculated by experts with experience in dosing children.
A posttreatment whole-body scan is recommended for all children 4 to 7 days after 131I therapy. The addition of single-photon emission CT with integrated conventional CT (SPECT/CT) may help to distinguish the anatomic location of focal uptake.
While rare, late effects of 131I treatment include salivary gland dysfunction, bone marrow suppression, pulmonary fibrosis, and second malignancies.[5]
Spinelli C, Strambi S, Rossi L, et al.: Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients. J Endocrinol Invest 39 (9): 1055-9, 2016.
Machens A, Elwerr M, Thanh PN, et al.: Impact of central node dissection on postoperative morbidity in pediatric patients with suspected or proven thyroid cancer. Surgery 160 (2): 484-92, 2016.
Albano D, Bertagna F, Panarotto MB, et al.: Early and late adverse effects of radioiodine for pediatric differentiated thyroid cancer. Pediatr Blood Cancer 64 (11): , 2017.
Treatment of Recurrent Papillary and Follicular Thyroid Carcinoma
Despite the more advanced disease at presentation compared with adults, children with differentiated thyroid cancer generally have an excellent survival with relatively few side effects.[1,2,3]
Treatment options for recurrent papillary and follicular thyroid carcinoma include the following:
Radioactive iodine ablation with iodine I 131 (131I).
Radioactive iodine ablation with 131I is usually effective after recurrence.[4] For patients with 131I-refractory disease, molecularly targeted therapies using kinase inhibitors may provide alternative therapies.
Tyrosine kinase inhibitors (TKIs) with documented efficacy for the treatment of adults include the following:
Sorafenib. Sorafenib is a vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and RAS kinase inhibitor. In a randomized phase III trial, sorafenib improved progression-free survival (PFS) when compared with placebo (10.8 months vs. 5.8 months) in adult patients with radioactive iodine–refractory locally advanced or metastatic differentiated thyroid cancer.[5] Sorafenib was approved by the U.S. Food and Drug Administration (FDA) in November 2013 for the treatment of adults with late-stage metastatic differentiated thyroid carcinoma.
Pediatric-specific data are very limited; however, in one case report, sorafenib produced a radiographic response in a patient aged 8 years with metastatic papillary thyroid carcinoma.[6]
Lenvatinib. Lenvatinib is an oral VEGFR, fibroblast growth factor receptor, PDGFR, RET, and KIT inhibitor. In a phase III randomized study of adults with 131I-refractory differentiated thyroid cancer, lenvatinib was associated with a significant improvement in PFS and response rate when compared with a placebo.[7] Lenvatinib was approved by the FDA in February 2015 for the treatment of adults with progressive radioactive iodine–refractory differentiated thyroid carcinoma.
Three children with papillary thyroid carcinoma who were refractory to radioactive iodine had a clinical response to lenvatinib.[8]
BRAF inhibitors. In an open-label, nonrandomized phase II study of vemurafenib in adult patients with 131I-refractory metastatic or unresectable BRAF V600E–positive papillary thyroid carcinoma who had not been previously treated with a TKI, a response rate of 38.5% was documented.[9] For patients with metastatic or advanced BRAF V600E–mutated anaplastic thyroid carcinoma, the combination of dabrafenib with the MEK inhibitor trametinib has shown a response rate of 69%.[10]
Larotrectinib and entrectinib (NTRK inhibitors). Larotrectinib (a targeted therapy) has been used to treat patients with TRK fusion–positive thyroid carcinoma. Five of five patients with TRK fusion–positive thyroid carcinomas who were treated with larotrectinib therapy achieved partial or complete responses.[11] Responses to entrectinib have also been reported.[12] Larotrectinib and entrectinib have been approved by the FDA for the treatment of adults and children (restricted to patients older than 12 years for entrectinib) with solid tumors that include the following characteristics:[13]
Have an NTRK gene fusion without a known acquired resistance mutation; and
Are metastatic or for which surgical resection is likely to result in severe morbidity; and
Have no satisfactory alternative treatments or that have progressed following treatment.
Selpercatinib (a RET inhibitor). In a phase I/II trial of selpercatinib therapy for patients (age range, 25–88 years) with RET-mutant cancers, 19 patients with RET fusion–positive, previously treated thyroid cancers were enrolled.[14]
Fifteen of 19 patients (79%) achieved an objective response (1 complete response and 14 partial responses), and the median duration of response was 18.4 months.
The most common grades 3 to 4 treatment-related adverse events were hypertension (12%), increased alanine aminotransferase (ALT) (10%) and aspartate aminotransferase (AST) (7%), diarrhea (3%), and prolonged QT interval (2%).
Selpercatinib was approved by the FDA (under accelerated approval) for the treatment of adult and pediatric patients aged 12 years and older with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine–refractory (if radioactive iodine is appropriate).[15]
(Refer to the PDQ summary on Thyroid Cancer Treatment [Adult] for more information.)
Treatment Options Under Clinical Evaluation for Recurrent Papillary and Follicular Thyroid Carcinoma
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
APEC1621G (NCT03220035) (Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations [A Pediatric MATCH Treatment Trial]): This phase II pediatric MATCH trial studies how well vemurafenib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with BRAF V600 mutations that have spread to other places in the body (advanced) and have come back (recurrent) or do not respond to treatment (refractory).
APEC1621N (NCT04320888) (Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial): This phase II pediatric MATCH trial studies how well selpercatinib works in treating patients with solid tumors that have spread to other places in the body (advanced), lymphomas, or histiocytic disorders that have activating RET gene alterations.
Powers PA, Dinauer CA, Tuttle RM, et al.: Treatment of recurrent papillary thyroid carcinoma in children and adolescents. J Pediatr Endocrinol Metab 16 (7): 1033-40, 2003.
Brose MS, Nutting CM, Jarzab B, et al.: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384 (9940): 319-28, 2014.
Iyer P, Mayer JL, Ewig JM: Response to sorafenib in a pediatric patient with papillary thyroid carcinoma with diffuse nodular pulmonary disease requiring mechanical ventilation. Thyroid 24 (1): 169-74, 2014.
Schlumberger M, Tahara M, Wirth LJ, et al.: Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372 (7): 621-30, 2015.
Mahajan P, Dawrant J, Kheradpour A, et al.: Response to Lenvatinib in Children with Papillary Thyroid Carcinoma. Thyroid 28 (11): 1450-1454, 2018.
Brose MS, Cabanillas ME, Cohen EE, et al.: Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol 17 (9): 1272-82, 2016.
Subbiah V, Kreitman RJ, Wainberg ZA, et al.: Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 36 (1): 7-13, 2018.
Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018.
Chu YH, Dias-Santagata D, Farahani AA, et al.: Clinicopathologic and molecular characterization of NTRK-rearranged thyroid carcinoma (NRTC). Mod Pathol 33 (11): 2186-2197, 2020.
Bayer HealthCare Pharmaceuticals: VITRAKVI (larotrectinib): Prescribing Information. Stamford, Conn: Loxo Oncology, Inc., 2018. Available online. Last accessed September 28, 2020.
Wirth LJ, Sherman E, Robinson B, et al.: Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med 383 (9): 825-835, 2020.
Eli Lilly and Company: RETEVMO (selpercatinib): Prescribing Information. Indianapolis, Ind: Lilly USA, LLC, 2020. Available online. Last accessed September 28, 2020.
Treatment of Medullary Thyroid Carcinoma
Medullary thyroid carcinomas are commonly associated with the multiple endocrine neoplasia type 2 (MEN2) syndrome (refer to the PDQ summary on Childhood Multiple Endocrine Neoplasia [MEN] Syndromes Treatment for more information).
Treatment options for medullary thyroid carcinoma include the following:
Surgery: Treatment for children with medullary thyroid carcinoma is mainly surgical. Investigators have concluded that prophylactic central node dissection should not be performed on patients with hereditary medullary thyroid cancer if their basal calcitonin serum levels are lower than 40 pg/mL.[1]
Most cases of medullary thyroid carcinoma in children occur in the context of the MEN2A and MEN2B syndromes. In those familial cases, early genetic testing and counseling is indicated, and prophylactic surgery is recommended for children with the RET germline mutation. Strong genotype-phenotype correlations have facilitated the development of guidelines for intervention, including screening and age at which prophylactic thyroidectomy should occur.[2]
A retrospective analysis identified 167 children with RET mutations who underwent prophylactic thyroidectomy; this group included 109 patients without a concomitant central node dissection and 58 patients with a concomitant central node dissection. Postoperative hypoparathyroidism was more frequent in older children (32% in the oldest age group vs. 3% in the youngest age group; P = .002), regardless of whether central node dissection was carried out. Three children developed recurrent laryngeal nerve palsy, all of whom had undergone central node dissection (P = .040). All complications resolved within 6 months. Postoperative normalization of calcitonin serum levels was achieved in 114 of 115 children (99.1%) with raised preoperative values. Children were classified into risk groups by their specific type of RET mutation (refer to Table 1).[3]
In the highest-risk category, medullary thyroid carcinoma was found in five of six children (83%) aged 3 years or younger.
In the high-risk category, medullary thyroid carcinoma was present in 6 of 20 children (30%) aged 3 years or younger, 16 of 36 children (44%) aged 4 to 6 years, and 11 of 16 children (69%) aged 7 to 12 years (P = .081).
In the moderate-risk category, medullary thyroid carcinoma was seen in one of nine children (11%) aged 3 years or younger, 1 of 26 children (4%) aged 4 to 6 years, 3 of 26 children (12%) aged 7 to 12 years, and 7 of 16 children (44%) aged 13 to 18 years (P = .006).
The American Thyroid Association has proposed the following guidelines for prophylactic thyroidectomy in children with hereditary medullary thyroid carcinoma (refer to Table 1).[2]
Table 1. Risk Levels and Management Based on CommonRETMutations Detected on Genetic Screeninga
Medullary Thyroid Carcinoma Risk Level
Highest (MEN2B)
High (MEN2A)
Moderate (MEN2A)
MEN2A = multiple endocrine neoplasia type 2A; MEN2B = multiple endocrine neoplasia type 2B.
a Adapted from Wells et al.[2]
RET Mutation M918T A883F, C634F/G/R/S/W/Y G533C, C609F/G/R/S/Y, C611F/G/S/Y/W, C618F/R/S, C620F/R/S, C630R/Y, D631Y, K666E, E768D, L790F, V804L, V804M, S891A, R912P
Age for Prophylactic Thyroidectomy Total thyroidectomy in the first year of life, ideally in the first months of life. Total thyroidectomy at or before age 5 y based on serum calcitonin levels. Total thyroidectomy to be performed when the serum calcitonin level is above the normal range or at convenience if the parents do not wish to embark on a lengthy period of surveillance.
Tyrosine kinase inhibitor (TKI) therapy: A number of TKIs have been evaluated and approved for patients with advanced thyroid carcinoma.
Vandetanib. Vandetanib (an inhibitor of RET kinase, vascular endothelial growth factor receptor [VEGFR], and epidermal growth factor receptor signaling) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic or progressive medullary thyroid cancer in adult patients with unresectable, locally advanced, or metastatic disease. Approval was based on a randomized, placebo-controlled, phase III trial that showed a marked progression-free survival (PFS) improvement for patients randomly assigned to receive vandetanib (hazard ratio, 0.35); the trial also showed an objective response rate advantage for patients receiving vandetanib (44% vs. 1% for the placebo arm).[4,5]
Children with locally advanced or metastatic medullary thyroid carcinoma were treated with vandetanib in a phase I/II trial. Of 16 patients, only 1 had no response, and 7 had a partial response, for an objective response rate of 44%. Disease in three of those patients subsequently recurred, but 11 of 16 patients treated with vandetanib remained on therapy at the time of the report. The median duration of therapy for the entire cohort was 27 months, with a range of 2 to 52 months.[6] A long-term outcome evaluation in a cohort of 17 children and adolescents with advanced medullary thyroid carcinoma who received vandetanib reported a median PFS of 6.7 years and a 5-year overall survival of 88.2%.[7]
Cabozantinib. Cabozantinib (an inhibitor of the RET and MET kinases and VEGFR) has also shown activity against unresectable medullary thyroid cancer (10 of 35 adult patients [29%] had a partial response).[8] Cabozantinib was approved by the FDA in November 2012 for the treatment of adults with metastatic medullary thyroid cancer.
Selpercatinib (a RET inhibitor). A phase I/II trial of selpercatinib therapy for patients with RET-mutant cancers enrolled 55 patients with RET-mutant medullary thyroid cancer (age range, 17–84 years) who were previously treated with vandetanib and/or cabozantinib and 88 patients with RET-mutant medullary thyroid cancer (age range, 15–82 years) who were not previously treated with vandetanib or cabozantinib.[9]
For the previously treated cohort, 69% of patients achieved an objective response, and the median duration of response had not been reached, with a median follow-up of 14 months.
For the cohort of patients who were not previously treated, 73% of patients achieved an objective response, with a median duration of response of 22.0 months.
Selpercatinib was approved by the FDA (under accelerated approval) for the treatment of adult and pediatric patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy.[10]
(Refer to the PDQ summary on Childhood Multiple Endocrine Neoplasia [MEN] Syndromes Treatment and the Treatment for Medullary Thyroid Cancer [MTC] section in the PDQ summary on Genetics of Endocrine and Neuroendocrine Neoplasias for more information.)
Treatment Options Under Clinical Evaluation for Medullary Thyroid Carcinoma
Machens A, Elwerr M, Lorenz K, et al.: Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations. Br J Surg 105 (2): e150-e157, 2018.
Wells SA, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012.
Thornton K, Kim G, Maher VE, et al.: Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res 18 (14): 3722-30, 2012.
Fox E, Widemann BC, Chuk MK, et al.: Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin Cancer Res 19 (15): 4239-48, 2013.
Kraft IL, Akshintala S, Zhu Y, et al.: Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib. Clin Cancer Res 24 (4): 753-765, 2018.
Kurzrock R, Sherman SI, Ball DW, et al.: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 29 (19): 2660-6, 2011.
Changes to This Summary (09 / 17 / 2021)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added Sugino et al. as reference 7.
Added American Academy of Pediatrics as reference 2.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood thyroid cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
be discussed at a meeting,
be cited with text, or
replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Thyroid Cancer Treatment are:
Denise Adams, MD (Children's Hospital Boston)
Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
Stephen J. Shochat, MD (St. Jude Children's Research Hospital)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Thyroid Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thyroid/hp/child-thyroid-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389315]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.
Last Revised: 2021-09-17


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Lamps are fine for lizards but snakes do better with an Under Tank Heater, which will provide a hide spot of the proper temperature. The whole tank does not have to be hot just one little spot the snake can go to when it needs higher temps for digestion. When you install a UTH be sure to run it on a thermostat.
Kingsnakes are diurnal, meaning they are active during the day and sleep at night. So leaving the lamp on all the time would not be good.
In terms of temperament, I would recommend leaving your king completely alone for 5-7 days. Change the water, spot clean, but do not completely clean, the cage, and after the time is up you can try a feeding, and about a day or 2 after that try handling again.
Most kings are "flighty" (the getting away behavior you described) when young. So long as it does not develop into outright aggression (which it typically doesn't) it generally goes away with careful handling and general maturity. Kings calm down as adults.
Kings, like most colubrids, are oppurtunistic feeders, and switch to f/t with no problem, cal kings in the wild eat pretty much anything they can overpower, the switch shouldn't be a problem. Where'd you get the snake that they were feeding it live, and why?


There are many things to be grateful for: colourful autumn leaves, legs that work, friends who listen and really hear, fresh eggs, warm jackets, tomatoes, the ability to read, roses, our health, butterflies. What's on your list?
Long before there were therapists, there were family members. Grandpa and Aunt Jane listened, or gave us advice, or sometimes just told us to buck up. If family couldn't help, there were friends or a clergy member. But most likely, we were also warned not to broadcast our troubles, and many people suffered their emotional problems silently.
Times have changed, and so has society's acceptance of seeking help. The old stigma of being seen as weak or incapable is largely gone. This has been helped tremendously by many well-known writers, actors and politicians being open about their struggles with, and treatments for, everything from depression to chronic shoplifting. Going to a therapist is now seen as a sign of strength and willingness to take charge of one's life. Rather than proof that someone is "sick," it is a sign of good health to make a commitment to change.
You might be wondering what talking to a therapist will do that you can't get from talking to a dear friend or family member. "Therapy is a unique relationship and what makes it valuable sets it apart from friendships, working partnerships, family connections and love affairs," says Carl Sherman, author of How to Go to Therapy: Making the Most of Professional Help.
The Benefits of Yoga: Good for Mind and Body!
You've certainly heard time and again that yoga is good for you. All that stretching and breathing calms you down and makes you feel better. But other than "making you feel good," what are the health benefits associated with practicing yoga?
More often than not, we tend to perceive yoga as a meditation practice that helps us physically – to balance, to stretch, etc. But yoga is also a practice that improves the well-being of our mental state. In fact, "yoga" is derived from the same root as the word "yoke," referring to the process of yoking the mind and body together. It is in combining both of these that the most benefit is derived from the practice of yoga.
* Breathing: most of us breathe very differently than we should. As infants, we breathe in by expanding our bellies, and breathe out by retracting our bellies. As we age, we actually reverse this process, and we tend to breathe in a very shallow manner. In fact, we very rarely truly give any thought at all to how we breathe. Pranayama, a yoga breathing exercise, actually helps to give thought to "how" we breathe and teaches us how to do it properly.
* Muscle tone and strength: many yoga poses require you to support yourself and balance on your limbs. This in turn increases your strength. Thus, more strength equals stronger, leaner muscles.


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Cameroon: How Samuel Eto'o conquered Fecafoot
By Jeune Afrique
Posted on Tuesday, 21 December 2021 09:55, updated on Friday, 7 January 2022 15:51
Samuel Eto'o was elected head of Fecafoot on 11 December. © Maboup
Former international football player Samuel Eto'o has done everything in his power to thwart his powerful rivals' manoeuvres, including running communication campaigns, lobbying and political negotiations.
At first, it was mission impossible.
In the race to become president of Fecafoot, Samuel Eto'o was up against Fifa, which is increasingly scrutinising the heads of national federations. Gianni Infantino, Fifa's Italian-Swiss boss, would like the World Cup to be held every two years, whereas South Africa's Patrice Motsepe, his ally at CAF, wants the African Cup of Nations to take place every four years.
The two men are working together to launch an African Superleague. Furthermore, their two bodies do not want headstrong leaders to be appointed, as they would likely resist these unpopular ideas.
READ MORE Cameroon: 'I am an African soldier' says former football star Samuel Eto'o
The CAF secretary-general, Veron Mosengo, who is close to Infantino, tried to get Eto'o to withdraw from a meeting in Kinshasa back in November. Part of the Cameroonian regime also distrusted the former international footballer, who was finally elected on 11 December.
Against the system
It is true that Eto'o had nothing to fear from Paul Biya. The Cameroonian president has not forgotten that he used Eto'o's connections in 2017 to ensure that the CAN went ahead as planned, even though the CAF had been on the verge of cancelling it.
On the other hand, some prominent government members are concerned about how popular the former captain of the Lions Indomptables is. On 8 November, Eto'o met with Samuel Mvondo Ayolo, the director of the president's civil cabinet, who is also close to Franck Biya, the head of state's eldest son, who was presented as his possible successor. He had to assure everyone that his run for the Fecafoot presidency was not politically motivated.
READ MORE Why do African football players not reach European management positions?
Eto'o was also confronted with the Mohammed Iya system, which had been orchestrated by this former boss of Sodecoton, the most powerful agro-industry in the Great North (three regions), from his cell in Kondengui prison in Yaoundé. This network has controlled Fecafoot for over 20 years. It is made up of 12 regional delegates from the north and several other 'northern' delegates with different professions (club presidents, referees, coaches).
Their strength? They are known for standing together and unanimously voting for the candidate of their choice. Whoever is supported by the Great North is the favourite.
From his cell, Iya pulls the strings through Alim Konaté, who – until now – had been Fécafoot's all-powerful vice-president. This system is supported by several government ministers from the northern part of the country. They include Gabriel Mbairobe, the agricultural minister, who hosted a meeting in support of the outgoing president, Seidou Mbombo Njoya, at his home in Garoua on 3 December and Ibrahim Talba Malla, the minister of public contracts, who worked to strengthen Eto'o's rival.
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The race to transform
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Although he is not from the Far North, Paul Atanga Nji, the minister of territorial administration and decentralisation, has also worked hard to prevent the former international footballer from being elected. Even though the secretary-general of the services of the governor of the centre, Simon Ghislain Etsil, who was elected delegate of the East Region (won by Eto'o), did not attend the elective General Assembly, many see this as pressure from his supervisory minister. Several delegates from the English-speaking North-West also say they have received phone calls from 'Minatd'.
Finally, Yannick Noah was also against Eto'o's presidential bid. The former acted as an intermediary in the contract between the equipment manufacturer Le Coq Sportif and the Lions Indomptables, which planned to start off Njoya's second term by holding a series of concerts during the next CAN.
Communication plan and lobbying
To take on the system, the footballer relied on communication campaigns and lobbying. He hired the services of Mireille Fomekong, head of the communication agency Ascèse, which is based in Douala. The latter chose to play the people against the elite in order to oppose popular pressure to the individual interests of each of the 76 voting delegates.
Eto'o, who has extensive knowledge of ethno-regional geopolitics and has conducted a sociographic study, also negotiated directly and personally with the delegates. Furthermore, he managed to secure the support of political and business barons, such as billionaire Baba Ahmadou Danpullo, who stands out for being both Fulani and English-speaking.
READ MORE Football: Should the African Cup of Nations be held every four years?
The former Inter Milan striker is also backed by Ibrahim El Rachidine, who is not only Garoua's new lamido (traditional and religious leader) but also an enemy of the Hayatou family, from which his predecessor Alim Hayatou, who died on 5 April, came. This strategy was the best way to counter the enmity between Eto'o and Issa Hayatou, who never forgave the footballer for having supported Ahmad Ahmad during the election that kicked him out of CAF in 2017. As such, he managed to divide the 'northern' bloc and rally a dozen delegates to his cause.
From then on, the two candidates only had to fight for delegates from the other regions. In this game, Njoya knew that he could not compete with a contender who had travelled thousands of kilometres to convince voters of the need to change the leaders of Cameroonian football. More than 50% of them were replaced during this election.

redpajama_set_name: RedPajamaCommonCrawl


text:
Bipartisan Alliance
Bipartisan Alliance, a Society for the Study of the US Constitution, and of Human Nature, where Republicans and Democrats meet.
At low levels of video gaming time, gaming protects against gun violence; at high levels, it imprints gun-related behaviors and naturalizes them, a small effect; moral panic of video gaming is largely unsubstantiated
Videogames and guns in adolescents: Preliminary tests of a bipartite association. Ofir Turel. Computers in Human Behavior, March 29 2020, 106355. https://doi.org/10.1016/j.chb.2020.106355
• We propose a U-shaped association between video-gaming and gun-related behaviors.
• At low levels of video gaming time, video gaming displaces gun-related behaviors.
• At high levels, it imprints gun-related behaviors and naturalizes them.
• This can explain inconsistent past findings based on an assumed linear association.
• Moral panic over light to moderate video gaming is largely unsubstantiated.
Abstract: The possible role of video gaming in imprinting aggressive and specifically gun-related behaviors has been elusive, and findings regarding these associations have been inconsistent. We address this gap by proposing and testing a bipartite theory that can explain inconsistent results regarding the previously assumed linear association between videogames and gun-related behaviors. Our theory suggests that this association follows a U-shape. It posits that at low levels of video gaming time, video gaming displaces gun-related behaviors and shelters adolescents by keeping them occupied and by reducing opportunities and motivation to acquire guns. However, at some level of gaming time (because most popular games adolescents play include violent aspects), the assumed imprinting of aggressive behaviors overpowers the positive displacement force, and this trivializes and naturalizes gun-carrying behaviors, and ultimately increases motivation to obtain and carry guns. We tested this theory with two national samples of American adolescents (n1 = 24,779 and n2 = 26,543, out of which 403 and 378, respectively, reported bringing a gun to school in the last month). Multiple analyses supported the proposed U-shaped association. These findings show that the moral panic over video games is largely unsubstantiated, especially among light to moderate gamers.
Keywords: Video gamesTechnology and societyGunsAdolescentsImprinting hypothesisDisplacement hypothesis
Posted by BipartisanAlliance2 at 7:20 AM 0 comments
Patrician women loitering on dark streets, giving themselves to common passers-by; half-clad men molested by their mothers and sisters; effeminates soft as a rabbit and "languid as a limp penis"
True Greek orgy meant mystic loss of self. But in imperial Roman orgy, persona continued. The Roman decadent kept the observing Apollonian eye awake during Dionysian revel. More Alexandrian connoisseurship, here applied to the fashionable self. Eye plus orgy equals decadence. Salaciousness, lewdness, lasciviousness: such interesting hyperstates are produced by a superimposition of mind on erotic action. The west has pioneered in this charred crimson territory. Without strong personality of the western kind, serious decadence is impossible. Sin is a form of cinema, seen from a distance. The Romans, pragmatically adapting Greek ideas, made engineering out of eroticism too. The heir of Greek theater was not Roman theater but Roman sex. The Roman decadence has never been matched in scale because other places and times have lacked the great mass of classical forms to corrupt. Rome made daemonic music of gluttony and lust from the Dionysian body. The Maenadism absent from Roman cult became imperial ecstasy, mechanized greed.
Roman literature's sexual personae are in hectic perpetual motion. Greek aristocratic athleticism split in two in Rome: vulgar gladiatorship by ruffians and slaves, and leisure-class sexual adventurism, a sporting life then as now. As the republic ends, Catullus records the jazzy promiscuity of Rome's chic set. Patrician women loitering on dark streets, giving themselves to common passers-by. Half-clad men molested by their mothers and sisters. Effeminates soft as a rabbit and "languid as a limp penis." A sodomite waking with battered buttocks and "red lips like snow," mouth rimmed with last night's pasty spoils. The strolling poet, finding a boy and girl copulating, falls upon the boy from behind, piercing and driving him to his task. Public sex, it is fair to say, is decadent. Oh, those happy pagan days, romping in green meadows: one still encounters this sentimental notion, half-baked Keats. It is quite wrong. Catullus, like Baudelaire, savors imagery of squalor and filth. His moral assumptions remain those of republican Rome, which he jovially pollutes with degeneration and disease. His poetry is a torch-lit descent into a gloomy underworld, where we survey the contamination and collapse of Roman personae. Men and women are suddenly free, but freedom is a flood of superfluous energy, a vicious circle of agitation, quest, satiation, exhaustion, ennui. Moral codes are always obstructive, relative, and man-made. Yet they have been of enormous profit to civilization. They are civilization. Without them, we are invaded by the chaotic barbarism of sex, nature's tyranny, turning day into night and love into obsession and lust.
Catullus, an admirer of Sappho, turns her emotional ambivalence into sadomasochism. Her chills and fever become his "odi et amo," "I hate and I love." Her beloved maidens, fresh as orange flowers, become his cynical Lesbia, adulteress and dominatrix, vampiristically "draining the strength of all." The urban femme fatale dons the primitive mask of mother nature. Lesbia, the wellborn Clodia, introduces to Rome a depraved sexual persona that had been current, according to aggrieved comment of the Old Testament, for a thousand years in Babylon. Female receptivity becomes a sinkhole of vice, the vagina a collector of pestilence to poison Roman nobility and bring it to an end.
Catullus is a cartographer of sexual personae. His lament for the dying god Attis (Carmen 63) is an extraordinary improvisation on gender. Castrating himself for Cybele, Attis enters a sexual twilight zone. Grammatically, the poem refers to him as feminine. "I a woman, I a man, I a youth, I a boy": in this litany of haunting memory, Attis floats through a shamanistically expanded present tense of gender, all things and nothing. Like imperial Rome, he has been pitched into an ecstatic free fall of personae. Suspension of sexual conventions brings melancholy, not joy. He is artistically detached from ordinary life but feels "sterile." Attis is the poet himself, mutating through gender in a strange, new, manic world.
Ovid, bom forty years later, is the first psychoanalyst of sex. His masterpiece is aptly called Metamorphoses: as Rome changes, Ovid plunders Greek and Roman legend for magic transformations—man and god to animal and plant, male to female and back. Identity is liquid. Nature is under Dionysian spell; Apollo's contours do not hold. The world becomes a projected psyche, played upon by amoral vagaries of sexual desire. Ovid's encyclopedic attentiveness to erotic perversity will not recur until Spenser's Faerie Queene , directly influenced by him. His successors are Sade, Balzac, Proust, Krafft-Ebing, and Freud.
The Metamorphoses is a handbook of sexual problematics. There is Iphis, a girl raised as a boy who falls in love with another girl and is relieved of her suffering by being changed into a man. Or Caeneus, once the girl Caenis, who rejects marriage and is raped by Neptune. As compensation, she is changed into a man invulnerable to wounds, martial and sexual. According to the Homeric scholiast, Caeneus set up his spear as a phallic totem in the marketplace, prayed and sacrificed to it, and commanded people hail it as a god, angering Zeus. In Vergil's underworld, Aeneas sees Caeneus as a woman, the morphological ghost of her femaleness reasserting itself. Ovid's complications of violation and fetishism are theory, not titillation. The theme is our "double nature," his term for the centaurs who smother impenetrable Caeneus after a horrifying orgy of Maenadic pulverizations. Like Freud, Ovid constructs hypothetical models of narcissism and the will-to-power. His point of view comes from his position between eras. Sexual personae, in flux, allow him to bring cool Apollonian study to bear upon roiling Dionysian process.
In his lesser works, Ovid lightens Catullus' bitter sex war into parlor politics. In The Art of Love, he says the seducer must be shrewd and changeable as Proteus. This is the Roman Dionysus, metamorphic Greek nature reduced to erotic opportunism. Sex-change is a foxy game: the wise adulteress, counsels Ovid, transsexualizes her letters, turning "he" to "she." The empire diverted Roman conceptual energy into sex. So specialized is Martial's sexual vocabulary that it influenced modem medical terminology. Latin, an exact but narrow language, became startlingly precise about sexual activity. The Latinist Fred Nichols tells me that a verb in Martial, used in poetry for the first time by Catullus, describes the fluttering movement of the buttocks of the passive partner in sodomy. There were, in fact, two forms of this verb: one for males and another for females.
Classical Athens, exalting masculine athleticism, had no conspicuous sexual sadomasochists and street transvestites. The Roman empire, on the other hand, if we believe the satirists, was overrun by epicene creatures. Ovid warns women to beware of elegant men with coiffures "sleek with liquid nard"—they may be out to steal your dress! "What can a woman do when her lover is smoother than she, and may have more boyfriends?" 28 Ausonius tells a sodomist with depilated anus and buttocks, "You are a woman behind, a man in front." Girlish boys and long-haired male prostitutes appear in Horace, Petronius, and Martial. Gaius Julius Phaedrus blames homosexuals of both sexes on drunken Prometheus, who attached the wrong genitalia to human figures he was molding. Lesbianism, infrequent in Greek literature, makes a splash in Rome. Martial and Horace record real-life tribads, Baiba, Philaenis, and Folia of Arminum, with her "masculine libidinousness." There are lesbian innuendos about the all-woman rites of the Bona Dea, crashed by Publius Clodius in drag. Lucian's debater condemns lesbian acts as "androgynous passions" and calls dildos "infamous instruments of lust, an unholy imitation of a fruitless union ." 29 Rome's sexual disorientation was great theater, but it led to the collapse of paganism.
Pursuit of pleasure belongs on the party circuit, not in the centers of power. Today too, one might like playfulness and spontaneity in a friend, lover, or star, but one wants a different character in people with professional or political authority. The more regular, unimaginative, and boring the daily lives of presidents, surgeons, and airline pilots, the better for us, thank you very much. Hierarchic ministry should be ascetic and focused. It does not profit from identity crises, the province of art. Rome had a genius for organization. Its administrative structure was absorbed by the Catholic Church, which turned an esoteric Palestinian sect into a world religion. Roman imperial bureaucracy, an ex* tension of republican legalism, was a superb machine, rolling over other nations with brutal force. Two thousand years later, we are still feeling the consequences of its destruction of Judaea and dispersion of the fractious Jews, who refused to become Roman. We know from Hollywood movies what that machine sounded like, its thunderous, relentless marching drums pushing Roman destiny across the world and through history. But when the masters of the machine turned to idleness and frivolity, Roman moral force vanished.
The Roman annalists give us the riveting gossip. Sodomy was reported of the emperors Tiberius, Nero, Galba, Otho, Commodus, Trajan, and Elagabalus. Even Julius Caesar was rumored to be bisexual. Hadrian fell in love with the beautiful Antinous, deified him after his death, and spread his image everywhere. Caligula had a taste for extravagant robes and women's clothes. He dressed his wife Caesonia in armour and paraded her before the troops. He loved impersonations, appearing in wig and costume as singer, dancer, charioteer, gladiator, virgin huntress, wife. He posed as all the male and female gods. As Jupiter, he seduced many women, including his sisters. Cassius Dio tartly remarks, "He was eager to appear to be anything rather than a human being and an emperor ." 30 Nero chose the roles of bard, athlete, and charioteer. He dressed as a tragedian to watch Rome bum. Onstage he played heroes and heroines, gods and goddesses. He pretended to be a runaway slave, a blind man, a madman, a pregnant woman, a woman in labor. He wore the mask of his wife Poppaea Sabina, who had died, it was said, after he kicked her in her pregnant belly. Nero was a clever architect of sexual spectacle. He built riverbank brothels and installed patrician women to solicit him from doorways. Tying young male and female victims to stakes, he draped himself in animal skins and leapt out from a den to attack their genitals. Nero devised two homosexual parodies of marriage. He castrated the boy Sporus, who resembled dead Poppaea, dressed him in women's clothes, and married him before the court, treating him afterward as wife and empress. In the second male marriage, with a youth whom Tacitus calls Pythagoras and Suetonius Doryphorus, sex roles were reversed: the emperor was bride. "On the wedding night," reports Suetonius, "he imitated the screams and moans of a girl being deflowered ." 31
Commodus gave his mother's name to a concubine, making his sex life an Oedipal drama. He appeared as Mercury and transvestite Hercules. He was called Amazonius, because he dressed his concubine Marcia as an Amazon and wanted to appear as an Amazon himself in the arena. Elagabalus, Caracalla's cousin, brought the sexually freakish customs of Asia Minor to imperial Rome. He scandalized the army with his silks, jewelry, and dancing. His short reign was giddy with plays, pageants, and parlor games. Lampridius says, "He got himself up as a confectioner, a perfumer, a cook, a shopkeeper, or a procurer, and he even practiced all these occupations in his own house continually ." 32 Elagabalus' lordly ease of access to plebeian roles was social mobility in reverse. Like Nero, he practiced "class transvestism," David Reisman's phrase for the modem bluejeans fad . 33
Elagabalus' life passion was his longing for womanhood. Wearing a wig, he prostituted himself in real Roman brothels. Cassius Dio reports:
He set aside a room in the palace and there committed his indecencies, always standing nude at the door of the room, as the harlots do, and shaking the curtain which hung from gold rings, while in a soft and melting voice he solicited the passers-by. There were, of course, men who had been specially instructed to play their part. . . . He would collect money from his patrons and give himself airs over his gains; he would also dispute with his associates in this shameful occupation, claiming that he had more lovers than they and took in more money.
Miming an adulteress caught in the act and beaten by her husband, the emperor cherished black eyes as a souvenir. He summoned to court a man notorious for enormous genitals and greeted him with "a ravishing feminine pose," saying, "Call me not Lord, for I am a Lady." He impersonated the Great Mother in a lion-drawn chariot and publicly posed as the Venus Pudica , dropping to his knees with buttocks thrust before a male partner. Finally, Elagabalus' transvestite fantasies led to a desire to change sex. He had to be dissuaded from castrating himself, reluctantly accepting circumcision as a compromise. Dio says, "He asked the physicians to contrive a woman's vagina in his body by means of an incision, promising them large sums for doing so ." 34 Science, which only recently perfected this operation, is clearly laggard upon the sexual imagination.
Absolute power is a door into dreaming. The Roman emperors made living theater of their turbulent world. There was no gap between wish and realization; fantasy leapt into instant visibility. Roman imperial masque: charades, inquisition, horseplay. The emperors made sexual personae an artistic medium, plastic as clay. Nero, setting live Christians afire for a night banquet, played with reality. Roman copies of Greek statues are a bit dull and coarse. So too with Rome's sexual literalization of Greek drama. The emperors, acting to provoke, torture, or arouse, removed the poetry and philosophy from theater. The vomitoria of Roman villas are troughs for vomiting the last six courses before starting on the next. Vomitoria is also the name for the exits of Roman amphitheaters, through which the mob poured. Imperial Rome, heir to sprawling Hellenistic culture, suffered from too-muchness, the hallmark of decadence. Too much mind, too much body; too many people, too many facts. The mind of the king is a perverse mirror of the time. Having no cinema, Nero made his own. In Athens, the beautiful boy was an idealized objet de culte. In Rome, persons were stage machinery, mannequins, decor. The lives of the wastrel emperors demonstrate the inadequacy of our modem myth of personal freedom. Here were men who were free and who were sickened by that freedom. Sexual liberation, our deceitful mirage, ends in lassitude and inertness. An emperor's day was androgyny-in-action. But was he happier than his republican ancestors, with their rigid sex roles? Repression makes meaning and purpose.
Pandemics Depress the Economy, Public Health Interventions Do Not: Evidence from the 1918 Flu
Correia, Sergio and Luck, Stephan and Verner, Emil, Pandemics Depress the Economy, Public Health Interventions Do Not: Evidence from the 1918 Flu. SSRN, March 26, 2020. http://dx.doi.org/10.2139/ssrn.3561560
Abstract: What are the economic consequences of an influenza pandemic? And given the pandemic, what are the economic costs and benefits of non-pharmaceutical interventions (NPI)? Using geographic variation in mortality during the 1918 Flu Pandemic in the U.S., we find that more exposed areas experience a sharp and persistent decline in economic activity. The estimates imply that the pandemic reduced manufacturing output by 18%. The downturn is driven by both supply and demand-side channels. Further, building on findings from the epidemiology literature establishing that NPIs decrease influenza mortality, we use variation in the timing and intensity of NPIs across U.S. cities to study their economic effects. We find that cities that intervened earlier and more aggressively do not perform worse and, if anything, grow faster after the pandemic is over. Our findings thus indicate that NPIs not only lower mortality; they also mitigate the adverse economic consequences of a pandemic.
Keywords: 1918 Flu Pandemic, non-pharmaceutical interventions (NPI), real economy
JEL Classification: E32, I10, I18, H1
Mirror-writing intersects with fundamental questions about the neural representations for reading and writing, and for object recognition and purposeful action more generally
Reflecting on mirror-writing. Interviewing Robert McIntosh and Sergio della Sala. The Psychologist, April 2020 Vol.33 (pp.32-35), Mar 2020. https://thepsychologist.bps.org.uk/volume-33/april-2020/reflecting-mirror-writing
So, would it be normal for children to mirror-write?
Mirror-writing, though striking to see, is an absolutely normal occurrence when learning to write. It would surprise us if there are any children who never make at least some mirror reversals. Rather than being regarded as a mistake, mirror-writing can be viewed as an impressive act of generalisation from a child, who is able to produce mirrored forms that they have never been taught. Parents with a young child who mirror reverses letters or words should enjoy the variety, and should not worry. Such reversals would only be of concern if they persisted well beyond the age by which most children have securely learned letter direction (7-8 years), in which case they would be part of a broader profile of slow literacy development.
Is there any update on mirror-writing from your own research or other sources?
Mirror-writing is still a 'niche' research topic, but a few recent papers have been published on developmental mirror-writing. Jean Paul-Fischer's group in Lorraine (France) had previously shown that children learning a dextrad (left-to-right) language like French (or English) are much more likely to reverse characters that face to the left (like j, z, or 3) than those that face to the right (like k, s, or 6). They inferred that the child may implicitly learn that most letters they see face to the right, and then over-apply this rule, so that they are more likely to flip a left-facing character to the right than vice-versa. We recently confirmed that this bias really is driven by character orientation, and not by differences in frequency, or how hard it is to remember certain shapes. We taught primary school children to write four novel pseudo-letters, two of which were left-facing and two of which were right-facing. We used identical but mirror reflected character sets for different groups of children, to control for any incidental differences between the shapes. Children were three times more likely to mirror-write a novel character they had learned in a left-facing format than to mirror-write one they had learned in a right-facing format.
Interestingly, it turns out that the bias may not be so much about whether the character faces left or right, but whether it faces in the direction of writing. Fischer and his colleagues used a simple technique to bias children to start writing in a right-to-left (i.e. reversed) direction, and they found that the pattern of reversals was also reversed, so that right-facing letters were now more likely to be flipped than left-facing characters. So, it seems that children may generally learn to face characters in the direction of writing before they know which way each of the individual letters should face.
And there is one point in our previous article that we would now revise. We suggested that mirror-writing in children was driven mainly by uncertainty about the direction of writing actions, and not by perceptual uncertainty about how the letters should look on the page. We have now tested this idea more directly, and found that there is in fact a close relationship between a child's likelihood of mirror-writing and the errors they make when perceptually judging whether normal and reversed characters look correct or not. This relationship was significant even when controlling for age; and the letters that were most often mirror-written were also more prone to recognition errors. These new data indicate that perceptual uncertainty does accompany mirror-writing in children, and that visual and motor representations of letters develop in parallel.
What questions on mirror-writing are still unanswered?
One major shortcoming is that most of what we know about mirror-writing relates to dextrad (left-to-right) languages based on the Latin alphabet, which is only one class of directional writing system, so cross-cultural studies seem essential. How do these phenomena compare in other language systems, especially sinistrad (right-to-left) written languages such as Arabic or Hebrew? Bilingual children, being schooled both in dextrad and sinistrad languages, might be particularly interesting to study. We have unpublished data suggesting that children learning to read and write both English and Arabic make more orientation errors for left-facing characters in English and for right-facing characters in Arabic, consistent with a general bias to prefer letters that face in the script direction. It might also be interesting to examine the relation of reading and writing to other culturally-specified directional behaviours (such as turning taps or screws).
In adults, we would be interested to investigate a possible association of mirror-writing ability with atypical language dominance. We have functional magnetic resonance imaging data showing an unusual pattern of bilateral language representation in a skilled mirror writer. This result is intriguing, but it is not yet known whether it is typical of people who have a facility for mirror-writing. The extensive email correspondence that our Psychologist article has elicited has convinced us that there would be plenty of candidates for a larger-scale study. However, in pursuing this question it would be essential to define more precisely what should qualify a person as being a 'natural' mirror-writer; because mirror-writing is also a skill, like any other, that can be developed and made automatic through practice.
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