THYROID CANCER IN CHILDREN

Transcription

1 THYROID CANCER IN CHILDREN Isabel ROCA, Montserrat NEGRE Joan CASTELL HU VALL HEBRON BARCELONA

2 EPIDEMIOLOGY ADULTS males 1,2-2,6 cases / females 2,0-3,8 cases / ,02-0,3 / children 3-6% of all thyroid cancers 3rd most common solid tumor < 20 y 1.1 % cancer deaths only 8% die due to thyroid cancer rare in children below 16 y exceptional before 10 y Thyroid nodules in children and adolescents: although rare, have a higher rate of malignancy than in adults Feinmesser et al, J Ped End & Metab 1997; 10:

3 THYROID CANCER increase in incidence? American Society of Cancer, 2006 RISK FACTORS radiation INCREASE IN DIAGNOSTIC? screening US, cytology

4 1st INCIDENCE PEAK external neck irradiation for benign conditions Tinea capitis, acne, chronic tonsilitis, thymus enlargement 2nd INCIDENCE PEAK environmental contamination with radiactive iodine due to Chernobyl catastrophe in 1986 sharp increase in thyroid cancer incidence Mainly in children < 5 y at exposure Onset < 14 y MID 20th CENTURY EARLY 1990 s Children < 5 y Girls more than boys higher sensitivity to effects of ionizing irradiation

5 In most children thyroid cancer is already at an advanced stage of the disease at the moment of diagnosis However, in this age group, the outcome of thyroid cancer is good

6 Palpable thyroid nodules % Nodules in children are more often malignant than in adults > 4 cm: 36% children vs 15% adults < 1 cm: 9% children vs 22 adults Harness, 1992 Dottorini, 1997 Thompson, 2004

7 EPIDEMIOLOGY higher incidence in girls: ratio female / male 2:1 few cases under 5 years progressive increase with age: peak at puberty Vall Hebron series in children patients 3-18 years average 13.4 y +/-3.6 SD 28 boys 35 % (X 12 y) 52 girls 65 % (X 14 y) a 6a 8a 0a 2a 4a girls a boys years a

8 SEX AND AGE AT DIAGNOSIS Vall Hebron series <=10 y > 10 y Female 9 44 Male <5 y 5 y-6 y 7 y-8 y 9 y-10 y 11 y-12 y 13 y-14 y 15 y-16 y 17 y-18 y Female Male Under 10 years: girls = boys Overall incidence in females was higher than in males ( 2/1) Progressive increase of incidence with age, with peak at puberty, specialy in girls

9 SEX AND AGE AT DIAGNOSIS other series Female Male <10 >10 and <15 >15 Handkiewicz-Junak J Nucl Med 2007; 48:

10 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Poland 60% Barcelona Male Female 50% 40% 30% 20% Poland Barcelona 10% 0% <10 >10 and <15 >15

11 SEX AND AGE AT DIAGNOSIS different series 100% 80% 60% 40% 20% 0% Poland England France / Italy Belarous Poland 07 Barcelona Male 31% 35% 28% 38% 28% 35% Female 69% 65% 72% 62% 72% 65% < 15 years < 21 years < 21 years < 18 years < 18 years

12 HISTOLOGY different series 100% 80% 60% 40% 20% 0% Poland England France / Italy Belarous Poland 07 Barcelona Follicular 29% 23% 17% 6% 18% 16% Papillar 71% 77% 83% 94% 82% 84% < 15 years < 21 years < 21 years < 18 years < 18 years

13 16% THYROID CANCER IN CHILDREN HISTOLOGY Vall Hebron series Papillary Follicular papillary 84 % follicular 16 % <5y 5-6y 7-8y 9-10y 11-12y 13-14y 15-16y 17-18y papillary: o lymph node involvement +++ o lung metastases follicular o less lymph node involvement o fewer metastases

14 STAGING AT DIAGNOSIS VH series 56% of patients showed advanced disease at the moment of diagnosis: 63.7% lymph node involvement Stage I-II Stage III-IV 22.5% pulmonary metastasis CHILDREN ADULTS EXTRATHYROIDAL INVASION 24% 16% P 0,1 NECK NODE INVOLVEMENT 90% 35% P 0,001 DISTANT METASTASES 7% 2% P 0,001 Zimmerman, 1988 Thompson, 2004

15 Proven radiation: increase of thyroid cancer incidence in children and adolescents Data are compatible with experiences of the past after external exposure Projected number of cases for 50 years (Belarus) uncertainty range increase 80% above baseline

16 Center for THYROID TUMOURS MINSK paediatric patients Boys 279 Girls 461 Ratio 1 : 1,6 Mean duration follow-up : 96,6 months (1,5 220) 30 % (N=220) followed > 10 y 80 % (N=599) followed > 5 y Demidchik, 2006

17 THYROID CANCER in children and adolescent From Belarus after Chernobyl accident Median latent interval: 13 years Range 6-30 years Demidchick, 2003

18 THYROID CANCER in children and adolescent From Belarus after Chernobyl accident Dose and Relative Risk Median latent interval: 13 years Range 6-30 years Risk increases with radiation doses up to Gy Risk decreases at radiation doses > 30 Gy Acharya, 2003 Sigurdson, 2005

19 Children under the age of 1 at exposure show the highest susceptibility, and carry this risk with them into adult life Twenty years' experience with post-chernobyl thyroid cancer Best Pract Res Clin Endocrinol Metab (6):

20 4000 cases have been attributed to the accident, but so far very few have died. The risk falls rapidly with increasing age at exposure. Twenty years' experience with post-chernobyl thyroid cancer Best Pract Res Clin Endocrinol Metab (6):

21 THYROID CANCER STAGING

22 CLINICAL SYMPTOMS casual finding cervical mass: increased cervical perimeter 92 % 68 % thyroid nodules 25 % lymph nodes cervical lymph nodes % hoarness, dyspnea lung metastasis miliary 97% - nodular 3% almost always functional may not be detected on chest Xray or CT always detected on post 131 I therapy scan rarely other metastasis Vassilopoulou, 1993 Schlumberger, 1996 Ronga, 2004 Bal, 2004

23 CLINICAL SYMPTOMS casual finding cervical mass: increased cervical perimeter 92 % 68 % thyroid nodules 25 % lymph nodes cervical lymph nodes % hoarness, dyspnea lung metastasis miliary 97% - nodular 3% almos always functional may not be detected on chest Xray or CT always detected on post 131I therapy scan rarely other metastasis

24 STAGING AT DIAGNOSIS VH series 30 MEAN AGE INVERSE CORRELATION between: age at diagnosis stage YOUNGER = HIGHER STAGE N Stage 1 Stage 2 Stage 3 Stage 4 p = N Mean SD EE Stage ,53 + 2,615,675 Stage ,42 3,133,719 Stage ,35-3,334,654 Stage ,17 4,048,954

25 STAGING AT DIAGNOSIS different series 70% 60% 50% 40% 30% 20% 10% 0% Poland France / Italy Belarous Poland 07 Barcelona N1 58% 54% 65% 62% 65% M1 Stage IV 16% 17% 18% 13% 24%

26 CLINICAL SYMPTOMS VH series increased cervical perimeter 87,5% thyroid nodule 65,0% females 73,1% males 50,0% lymph nodes 22,5% females 11,5% males 42,9% increased cervical perimeter vs age < = 10 y 47,1% > 10 y 15,9% P = P = P = 0.024

27 PRONOSTIC FACTORS CHILDREN adult scoring systems are not valid CHILDREN AND ADOLESCENTS HAVE AN EXCELLENT LONG TERM PROGNOSIS WITH A LOW MORTALITY RATE DESPITE EXTENSIVE DISEASE WITH FREQUENT METASTATIC DISEASE AT PRESENTATION AND HIGHER RECURRENCE RATE

28 PRONOSTIC FACTORS TOTAL THYROIDECTOMY >>> less than total thyroidectomy Intergroup difference: P < Cox Mantel test Handkiewicz-Junak J Nucl Med 2007; 48:

29 PRONOSTIC FACTORS RADIOIODINE TREATMENT >>> no radioiodine treatment Intergroup difference: P < Cox Mantel test Handkiewicz-Junak J Nucl Med 2007; 48:

30 PRONOSTIC FACTORS NO LYMPH NODE METASTASES >>> lymph node mets or 1=unknown 2=LN neg 3=LN pos >>> status lymph nodes unknown Intergroup difference: 2 vs 3 P = Cox Mantel test Handkiewicz-Junak J Nucl Med 2007; 48:

31 PRONOSTIC FACTORS Cox Regression Analysis Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children (EJNM, 2000)

32 DIAGNOSIS echography with percutaneous aspirative punction thyroid scintigraphy ressection of a cervical lymph node differential diagnosis lymphoma tuberculosis Epstein Barr virus ricketsiosis abnormal thorax Xray : lung metastasis metastasis: lung and lymph nodes

33 TREATMENT 1 - SURGERY 2 - RADIOIODINE THERAPY 3 - HORMONAL SUPPRESSIVE THERAPY 4 - OTHERS: in some cases RADIOTHERAPY CHEMOTHERAPY

34 TREATMENT 1 - SURGERY Total (or near-total) thyroidectomy Frequent multifocality and bilaterality in papillary thyroid carcinoma Longer recurrence-free survival after total vs less than total thyroidectomy Lymphadenectomy: because frequent high staging or local involvement Routine dissection of central neck compartment Modified lateral neck dissection in case of proven laterocervical metastases Avoid radical neck dissection Jarzab, 2000 Thompson, 2004 Scheurmann, 1996

35 TREATMENT 1 - SURGERY 2 - RADIOIODINE THERAPY 3 - HORMONAL SUPPRESSIVE THERAPY 4 - OTHERS: in some cases RADIOTHERAPY CHEMOTHERAPY

36 TREATMENT VH series SURGERY Total or near-total thyroidectomy THYROID TREATMENT: ablative 131-Iodine therapy (mean individual dose of GBq) FOLLOW-UP: Serum thyroglobuline (Tg) level Whole body scan (WBS) Free of disease Tg < 2 ng/ml Negative WBS

37 SURGICAL COMPLICATIONS VH series 26 (32.5%) patients Mean age: 12.4 ± 3.8 years Directly related with: Advanced disease (p = 0.002) Papillary pattern (p = 0.007)

38 Use of rhtsh Paediatric rhtsh use to avoid hypothyroid morbidity TSH stimulation of rhtsh in children and adolescents the approved adult dosage appears to be well-tolerated in this population seems to be clinical safety reduced doses also may safely provide acceptable TSH stimulation Luster et al, 2009 J Clin Endocrinol Metab 94:

39 HU VALL HEBRON PROCEDURE Differenciated Thyroid Carcinoma Old protocol with high ablative doses: Doses: mci 131 I/week during 3 weeks WBS 4th day after every therapeutic dose L-Thyroxin to suppress TSH levels Whole-body scan (WBS): 5mCi 131 I

40 HU VALL HEBRON PROCEDURE Differenciated Thyroid Carcinoma Current protocol with low ablative doses: Single dose: mci 131 I under rhtsh Children < 30 kg: 2 doses rhtsh 0,5 Children > 30 kg: same as adults 7th day after therapeutic dose WBS SPECT-CT: improvement L-Thyroxin to suppress TSH levels Whole-body scan (WBS): 5mCi 123 I under rhtsh

41 Tg (rhtsh) > 1 ng/ml WBS / rhtsh RCT + Tg abnormal US and/or thorax xr with Tg > 1 ng/ml abnormal US and/or thorax xr with Tg < 1 ng/ml WBS and Tg + WBS neg and Tg + PAAF Treatment 131 I or Surgery Lesion detection: Doppler-US MRI PET under rhtsh

42 VALL HEBRON SERIES FOLLOW-UP Differences between both protocols Old protocol Current protocol P = NS No significant differences between both protocols PROTOCOL AGE Mean SEX female% HISTOLOGY papillary% Advanced Stage III-IV Follow-up (years) DOSE Mean high dose 12,7 ±4 63,00% 96,60% 55,00% 402±281 low dose 14,7 ±3 72,00% 77,77% 58,33% 174±102 Significance NS NS NS NS p < 0,001

43 VH series METASTASIS LUNG METASTASIS 23,8% initial stage 22,5% recurrence 1,2% Papillary 94,7% 123 I WBS All mets located in the lung 131 I post-treatment WBS

44 VH series LONG TERM FOLLOW-UP FOLLOW-UP > 2 y 87,5% MEAN 10,8 y RANGE 2 y - 24 y

45 VH series LONG TERM FOLLOW-UP free of disease persistent disease FIRST CONTROL 6 months 36,2% 63,8% END FOLLOW-UP 87,2% 12,9% RECURRENCES 10,0% local 85,7% lung mets 14,3%

46 VH series LONG TERM FOLLOW-UP Persistent Persistent disease disease Disease Disease Free Free Significance Significance MEAN MEAN AGE AGE 11,1 11,1 ±3,2 ±3, ±3,5 ±3,5 NS NS SEX SEX Persistent Persistent disease disease Disease Disease Free Free Significance Significance number number (f/m) (f/m) 4/4 4/4 43/17 43/17 % females females 50,00% 50,00% 71,00% 71,00% NS NS Persistent Persistent disease disease Disease Disease Free Free Significance Significance PAPILLAR PAPILLAR HISTOLOGY HISTOLOGY number number % 100,00% 100,00% 85,00% 85,00% P SEX 0,143 AGE 0,143 HISTOLOGY 0,584 NS NS

47 VH series LONG TERM FOLLOW-UP Initial Stage vs Status at the end of follow-up: pretreatment stage Total Stage 1 Stage 2 Stage 3 Stage 4 Recount % pretreatment stage % end follow-up % total Recount % pretreatment stage % end follow-up % total Recount % pretreatment stage % end follow-up % total Recount % pretreatment stage % end follow-up % total Recount % pretreatment stage % end follow-up % total End follow-up Free of Persistent disease disease Total ,0%,0% 100,0% 21,7%,0% 18,8% 18,8%,0% 18,8% ,1% 5,9% 100,0% 26,7% 11,1% 24,6% 23,2% 1,4% 24,6% ,3% 8,7% 100,0% 35,0% 22,2% 33,3% 30,4% 2,9% 33,3% ,5% 37,5% 100,0% 16,7% 66,7% 23,2% 14,5% 8,7% 23,2% ,0% 13,0% 100,0% 100,0% 100,0% 100,0% 87,0% 13,0% 100,0% p = 0.014

48 VALL HEBRON SERIES FOLLOW-UP Predictive Factors: STAGING Persistent disease Disease Free Total Stage I Stage II Stage III Stage IV Total number % 0,00% 5,50% 4,35% 42,85% 11,90% number % 100,00% 94,50% 95,65% 57,15% 88,10% number % 100,00% 100,00% 100,00% 100,00% 100,00% P = 0.003

49 VALL HEBRON SERIES FOLLOW-UP Predictive Factors: STAGING Persistent disease Disease Free Total Stage I-II-III Stage IV Total number % 3,80% 42,85% 11,90% number % 96,20% 57,15% 88,10% number % 100,00% 100,00% 100,00% P = 0.001

50 LONG TERM FOLLOW-UP Tg 6 month status at the end of follow-up: TG (6 month) Negative Recount End of follow-up Persistent Free of disease disease Total % TG at 6 month 100,0%,0% 100,0% Positive % end follow-up % total Recount 46,7%,0% 40,6% 40,6%,0% 40,6% % TG at 6 month 78,0% 22,0% 100,0% Total % end follow-up % total Recount 53,3% 100,0% 59,4% 46,4% 13,0% 59,4% % TG at 6 month 87,0% 13,0% 100,0% % end follow-up % total 100,0% 100,0% 100,0% 87,0% 13,0% 100,0% p = 0.009

51 LONG TERM FOLLOW-UP Tabla de contingencia Recurrence TG 6 month Negative Recount 0 1 Total % TG at 6 month 85,7% 14,3% 100,0% Positive % of Recurrence % total Recount 38,1% 66,7% 40,6% 34,8% 5,8% 40,6% % TG at 6 month 95,1% 4,9% 100,0% Total % of Recurrence % total Recount 61,9% 33,3% 59,4% 56,5% 2,9% 59,4% % TG at 6 month 91,3% 8,7% 100,0% % of Recurrence % total 100,0% 100,0% 100,0% 91,3% 8,7% 100,0% p = 0.214

52 123I- Post-surgery WB scan before treatment 131I- WB scan 7 days after treatment

53 IN SUMMARY THYROID CANCER IN CHILDREN Low prevalence Neck irradiation: predisposing factor The DTC is frequently associated with the presence of lymph nodes and distant metastasis (lung) at the moment of diagnosis

54 IN SUMMARY THYROID CANCER IN CHILDREN Recommendation: Total or nearly total thyroidectomy Central neck dissection 131 I ablation hormonal suppressive therapy

55 IN SUMMARY THYROID CANCER IN CHILDREN Relative mortality is very low Despite initial advanced disease Frequent recurrences Overall rather good prognosis

56 IN SUMMARY THYROID CANCER IN CHILDREN In children, the follicular type tends to be less agressive than the papillary

57 IN SUMMARY THYROID CANCER IN CHILDREN The initial stage IV is a bad prognosis factor A Tg value < 2 ng/ml measured postreatment (6 month) is a good prognosis factor due its association to: High rate of completely remission at the end of follow-up Low rate of recurrences

58 THANK YOU VERY MUCH FOR YOUR ATTENTION!