Incidence of anaplastic cancer


" Material and methods

"
Material"
§  Retrospective studies on ATC"

"
Methods"
§  Literature via PubMed (21 articles)"
"
§  French data"
§  Clinical presentation: French retrospective study "
TUTHYREF network and data collection from 5 hospitals
(n=403 cases)"
"
§  Incidence rates : 9 French registries (280 cases) FRANCIM
network"
"
"
 Pathological aspects of ATC"
An off-white, fleshy large thyroid tumor with necrosis and
hemorrhage, infiltration of extrathyroidal tissues "

- ATC without DTC : arise de novo"

- ATC with concomitant DTC : 80% (including Hürthle cells variants)"
- ATC arising from DTC through clonal transformation of DTC"
"
Risk factor : Iodination of salt=> decrease of ATC"
Roche 2010, Ain 1998, Besic, Han 2012 !
 Pathological features of ATC"
Spindle cell 53%, giant cell 46-50%, squamoid cell 7-19%"
"
HES coloration:"
Spindle cells"
Eosinophile cyto"
Large nuclei"

≠ diagnosis:"
"
-  Sarcoma"
-  Riedel"
"
"
Anti AE1AE3 +" Anti Tg -"
Immunohistochemistry of ATC: varied results"
Positive staining for Tg 0-55%, vimentin 23-94%, keratins 12-80%"
Tissier courtesy!
Incidence trends of thyroid cancer by 

histological type (1973-02) in the U.S."

Increase in papillary type over a 20-year period x 5.2 in M, x 5.7 in F"

Medullary and ATC categories combined into a single category “poor DTC”"
Incidence of ATC stable (p>0.2 for trend), no change in the mortality"
Davies, SEER program, JAMA 06
 Incidence rates by histological type

Incidence of ATC 1-2 cases per million population per year"

Cancer incidence in 5 continents 1998-2002, females: Kilfoy,Cancer Causes Control 2009
 Incidence trends of ATC in Italy

1985-1994 (n= 193) and 1995-2004 (n= 307)"

3.7% à1%"

Italian Network of Cancer Registries"

Retrospectives analysis of 500 thyroid cancers diagnosed over 20 yrs"
Reduction of mortality rate of 4% per year"
Trimboli Thyroid 2006
 Incidence trends of ATC

(1989-2009) in France"
incidence  rate/100.000/yr   0,3  

0,25  

0,2  

0,15  

0,1  

0,05  

0  
1989  
1990  
1991  
1992  
1993  
1994  
1995  
1996  
1997  
1998  
1999  
2000  
2001  
2002  
2003  
2004  
2005  
2006  
2007  
2008  
2009  
years  

Slight decrease in incidence rate of ATC over the 2 last decades"

Calvados, Doubs, Hérault, Isère, Bas-Rhin, Haut Rhin, Somme, Tarn, Marne
Ardennes registries (280 cases) !
9 registries, FRANCIM data 2012
 ATC incidence by age in France

Incidence  *10    
0,08  

0,07  

0,06  

0,05  

0,04  

0,03  

0,02  

0,01  

0  
[00;04]   [10;14]   [20;24]   [30;34]   [40;44]   [50;54]   [60;64]   [70;74]   [80;84]  

20-24 years old: Incidence" "0.00021"

80-84 " " " "0.003" 9 registries, FRANCIM data 2012
"
 Female-to-male F/M age-specific thyroid
cancer incidence rate ratios (IRR)
by type and racial/ethnic group

In PTC and FTC, F/M IRR among whites decreased"

with age"
In anaplastic ones, "
-  F/M IRR = 1 in old ages"
-  F/M IRR <1 in tumors > 4 cm"
-  Elevated F/M ratio only for regional stage disease"
SEER-13 data 1998-2002, females Aschebrook – Kilfoy Thyroid 2012
 Age-specific thyroid cancer incidence by
type and racial/ethnic group in females

For PTC: similarity among the racial/ethnic groups"

Lower rate for black women at all ages"
Rate for anaplastic rose rapidly later in life"
Highest among Hispanics 0.17/100.000 woman-yrs"
and among Asians in men 0.11/100.000 man-yrs"
SEER-13
" data 1998-2002, females Aschebrook - Kilfoy,Cancer Thyroid 2012
 Clinical presentation"

The concept of the rapid clinical course is widely recognized"

Rapidly enlarging throat mass, with compressive symptoms"
Often discover at a stage of regional extension or metastasis (50%) "
Roche, Annal Endocrinol 2010!
 Clinical aspects of ATC"
Kebebew Kim" Akaishi" Han" French
2005" 2007" 2011" 2012" Data
2012"

Number of cases" 516" 121" 100" 95" 403"

Average age (yr)" 71.3" 64" 68" 64.7" 70"
Sex ratio (M/F)" 1/2" 1/1,9" 1/4" 1/3" 1/0,6"
Tumor size(mm)" 64" 55" >50 in 53" 67"
21%"

Compressive -" -" 48" -" 31.4"

symptoms (%)" "
N1 (%)" 37,6" 57" -" 38"
Distant metastasis" 43" 24" 58" -" 53"
Surgery (%)" 49" -" 70" 54" 68"
Radiotherapy (%)" 63" -" 78" -" 50"
Chemotherapy (%)" -" -" 27" -" 45"
Time trend in tumour size of anaplastic carcinoma"
Total = 95 ATC" 1995-99" 2000-04" 2005-10" P
n=29" n=37" n=29" value"
Mean age (yr)" 65.1" 63.2" 62.7" NS"
Female %" 69.0" 78.4" 79.3" NS"
ECOG %" " " " NS"
0-1" 44.8" 51.4" 65.5"
2-4" 55.2" 48.6" 34.5"
Pre-existing MNG" 31.0" 43.2" 27.6" NS"
Size (cm) mean (SD)" 6.2 (2.3)" 5.5 (3.2)" 4.0 (3.1)" 0.016"
" " " "
ATC ≤ 1cm %" 0" 2.7" 31"
Metastasis at Dg %" 44.8" 32.4" 41.4" NS"
Pathology %" " " " 0.019"
ATC without DTC" 89.7" 64.9%" 51.7%"
ATC with concomit. DTC" 0" 8.1%" 13.8%"
ATC arising from DTC" 10.3" 27.0%" 34.5%"
"

Extrathyr extension %" 55.2%" 64.9" 58.6" NS"

adapted from Han, retrospective study from 2 Korean hospitals Clin Endocrinol 2012 !
 Time trend in tumour size of anaplastic carcinoma"

The mean tumor size"

decreased overtime"

15/95 pts survived "

more than 2 years"
"
9/15 had tumour< 1cm"
« arising from DTC »"

1995-99" 2000-04" 2005-10"

adapted from Han, retrospective study from 2 Korean hospitals Clin Endocrinol 2012 !
Time trend in ultrasonography : unilobar form?

Better survival ?"

Elastographic study: stiffness and heterogeneity

Shear wave technic"

CT scan is helpful in staging
disease"

Upper mediastinal area"

Endotracheal tumor"
"
 Value of 18F-FDG PET/CT"
§  17% of thyroid lesions"
§  56% of cervical lymph nodes"
"
§  77% of mediastinal lymph nodes"
"
§  4% of lung metastases"
§  100%" of bone metastases "
§  33% "of liver metastases "
§  50% of adrenal metastases "
35% of involved organs were revealed only
by PET/CT (and not by CT)"
Treatment is modify in 25% of cases"

Sensitivity" All Thyroid Cervical Mediastinal Lung" Bone" Other

lesions" tumor" lymph nodes" lymph nodes" lesions"
TEP-FDG" 99.6%" 100%" 100%" 100%" 100%" 100%" 88%"
CT scan" 62%" 83" 44%" 33%" 96%" 0%" 50%"
p! < 0.02! < 0.2! < 0.025! < 0.03! < 0.23! < 0.015! < 0.12!

Poisson, Eur J Nucl Med 2010

20 pts, 265 lesions in 63 organs"
 Prognostic significance of

initial 18F-FDG PET/CT"
Functional volume of FDG uptake (≥300 ml) "
"
Intensity of FDG uptake (SUVmax ≥18)"
" "
"
"

20 pts, 265 lesions in 63 organs" Poisson, Eur J Nucl Med 2010

 Median of survival time

4-12 months"
Months"

The rare ATC with apparent long term survival are "
- Younger"
-  Have small primary foci of localized ATC"
-  Have been aggressively treated "
"
 Causes of death

"

The aggressive nature and rarity of ATC makes it difficult "

to compare patients outcomes"
"
-  Local compression of the upper airways"
-  Distant extension of the disease"
-  Poor general condition"
-  Cardiac events or complications of radiotherapy"