carcinoma diﬀerenziato tiroideo le linee guida … diﬀerenziato tiroideo le linee guida nella...

Rimini,5-8novembre2015


PaciniF,PapiniE,BellantoneR,SalvatoriM&Frasolda@A

CarcinomaDifferenziatoTiroideoLelineeguidanellareal-life


Aisensidell’art.3.3sulconfliOodiinteressi,pag17delRegolamentoApplica@voStato-Regionidel5/11/2009,dichiarochenegliul@mi2anninonhoavutorilevan@rappor@direTdifinanziamentoconsoggeTportatoridiinteressicommercialiincamposanitario.

Conflitti di interesse


•  Emanuela, age 51 •  Shop manager in fashion outlet - No children •  Clinical history: thoracic trauma after car

accident 15 years ago •  Currently asymptomatic •  Thyroid US exam during a medical check up.

Clinicalcase1.


Clinicalcase1:EmanuelaRimini,5-8novembre2015


US Report

•  Normal Thyroid size

•  Left thyroid lobe: in the upper third, small (7.5 mm Ø)

hypoechoic nodule with slightly irregular margins

•  Right thyroid lobe: no nodules - homogeneous gland

tissue

•  No enlarged neck lymph nodes.


Clinical and Lab data

•  Thyroid nodule is not clinically evident, neither at palpation nor at inspection

•  No thyroid disease in Emanuela’s family

•  TSH: 2.3 µU/ml

•  US-guided FNA is performed


FNA report

“Solid aggregates of thyroid epithelial cells. Focal nuclear dysmetria and occasional nuclear grooves”

Tir5


Surgery or

Wait-and-see strategy?

Question 1.


FNA evidence of thyroid malignancy

•  If a cytology result is diagnostic for primary thyroid malignancy, surgery is generally recommended.

•  An active surveillance management approach can be considered as an alternative to immediate surgery in patients with very low risk tumors

(Strong recommendation, Moderate-quality evidence)


Question 1 Surgical treatment or a wait-and-see strategy?

[D3] Active surveillance of DTC primary tumors

Ito, Miyauchi et al. 2010; Sugitani, Toda et al. 2010

have provided compelling data that an active surveillance

management approach to papillary microcarcinoma is a

safe and effective alternative to immediate surgical

These data have led to Recommendation 8E that

FNA is not required for suspicious thyroid nodules < 1 cm

without other high risk features and Recommendation

12A which allow for active surveillance of primary

tumors provided they could be classified as “very low risk

tumors.”


n° 340 patients


If surgery, total thyroidectomy (+ CND?) or lobectomy?

Question 2.


Operative approach for differentiated thyroid cancer

If surgery is chosen for patients with thyroid cancer <1 cm without extrathyroidal extension and cN0, the initial surgical procedure should be a thyroid lobectomy unless there are clear indications to remove the contralateral lobe. (Strong Recommendation, Moderate-quality evidence)


Operative approach for differentiated thyroid cancer

Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas in the absence of prior head and neck irradiation, familial thyroid carcinoma, or clinically detectable cervical nodal metastases. (Strong Recommendation, Moderate-quality evidence)


Question 2: what kind of surgery

In properly selected patients, clinical outcomes are very similar following unilateral or bilateral thyroid surgery. •  More selective approach to RAI ablation. •  The presence of the remaining lobe of the gland may obviate the life-long need for

exogenous thyroid hormone therapy. •  Reliance on neck ultrasonography and serial serum Tg measurements. Evidence: •  Bilimoria et al: 52,173 PTC (National Cancer Data Base 43,227 total

thyroidectomy, 8,946 lobectomy), similar 10 year overall survival (98.4% vs 97.1%) and 10 year recurrence rate (7.7% vs 9.8%).

•  Haigh et al: 5,432 PTCs (SEER data based 4,612 total thyroidectomy and 820 lobectomy): no difference in 10 year overall survival.

•  Barney et al SEER database: 23,605 DTC (12, 598 total thyroidectomy, 3,266 lobectomy): no difference in 10 year cause specific survival (96.8% vs 98.6).

•  Mendelsohn et al: 22,724 PTC (16,760 total thyroidectomy, 5,964 lobectomy): no difference in disease specific survival.


And the other Guidelines?

Question 1. & 2.


Lobectomy may be considered when all the following are present: •  Age 15 – 45 yrs •  No prior irradiation •  No distant metastasis •  No cervical node metastasis •  No extrathyroidal extension •  Tumor < 4 cm in diameter •  No aggressive variant


Management of papillary microcarcinoma

Thyroid lobectomy is recommended for patients with a unifocal microPTC and no other risk factors.

British Thyroid Association Guidelines for the Management of Thyroid Cancer



Total thyroidectomy is recommended for patients with:

- microPTC and familial non-medullary thyroid cancer

- multifocal microPTC involving both lobes.




For all other patients with microPTC, recommendation for type of surgery should be based on consideration of risk factors and Personalised Decision Making is recommended.



What is the Experts’ Opinion?

Question 1. & 2.


•  Danica, age 33, born in Romania, Italy since 2007

•  Tenderness and discomfort in her neck and

appearance of a lump on the right side

•  No familial thyroid disease - no irradiation

•  TSH 1.45 mU/ml

•  Referred by her GP for thyroid US exam.

Clinicalcase2:Danica


Clinicalcase2:DanicaRimini,5-8novembre2015


US Report

•  Normal Thyroid size. Mildly inhomogeneous tissue

•  Right thyroid lobe: large (29 x 17 x 21 mmØ)

hysoechoic solid nodule, slightly irregular but well

defined margins. Peri- and intra-nodular

vascularization.

•  Left thyroid lobe: no nodules

•  No evidence of enlarged neck lymph nodes.


FNA Report

«Follicular and microfollicular aggregates of thyrocytes with mild anysocariosis. Scarce colloid. Follicular neoplasm» .

TIR3B (SIAPEC) - Thy-3f (BTA)


Case 2- Surgical treatment

•  Danica undergoes right lobectomy

•  Histologic Report: «Papillary thyroid cancer, follicular variant, 28 mm diameter. Minimal infiltration of the thyroid capsule without clear extension into soft tissues Surgical margins free of disease. No vascular invasion» pT2 pNx R0

•  TSH: 4.7 uU/ml


Completion thyroidectomy?

Question n.3


Completion thyroidectomy

•  Completion thyroidectomy should be offered to those patients for whom a bilateral thyroidectomy would have been recommended had the diagnosis been available before the initial surgery.

•  Therapeutic central neck lymph node dissection should be included if the lymph nodes are clinically involved.

(Strong Recommendation, Moderate-quality evidence)


•  For patients with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cN0), the initial surgical procedure can be either a bilateral procedure (near-total or total thyroidectomy) or a unilateral procedure (lobectomy).

Surgery for FNA evidence of thyroid malignancy


•  Thyroid lobectomy alone may be sufficient initial treatment for low risk papillary and follicular carcinomas; however, the treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow-up based upon disease features and/or patient preferences.

(Strong Recommendation, Moderate-quality evidence)

Surgery for FNA evidence of thyroid malignancy


Question 3: completion thyroidectomy

•  This case has the features of a low risk intrathyroidal tumor.

•  Such PTCs can be managed with either lobectomy or total thyroidectomy.

•  Thus, a completion thyroidectomy is not required.



Question 3


Observe without completion thyroidectomy if all the following are present: •  Tumor < 1 cm in diameter •  No cervical node metastasis •  No contralateral lesion •  Complete surgical resection


Therapeutic surgery for thyroid cancer

•  Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter, or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extra-thyroidal spread (pT3 and pT4a), familial disease, and those with clinically or radiologically involved nodes and/or distant metastases.



Therapeutic surgery for thyroid cancer

In patients with unifocal tumours >1 – ≤4 cm in diameter, age <45 years, with no extrathyroidal spread, no familial disease, no evidence of lymph node involvement, no angioinvasion and no distant metastases, the advantage of total thyroidectomy vs. emithyroidectomy is unclear. In such cases Personalised Decision Making is recommended.



Additional risk factors which may swing the balance in favour of Total Tx

•  Size > 2 cm - PET positive* •  Poorly differentiated component •  Radiation-induced cancer.




Question 3.


Case 2: Danica (follows!)

•  Danica asks for undergoing completion thyroidectomy

•  Histologic Report «Left thyroid lobe. Normal thyroid tissue. No neoplastic foci in the resected lobe».


RAI ablation?

Question 4.


EvidenceofDiseasespecificsurvival

EvidenceofDiseasefreesurvival

RAIindicated


EvidenceofDiseaasespecificsurvival

EvidenceofDiseaasefreesurvival

RAIindicated


Question 4 RAI ablation

•  Schvartz, J Clin Endocrinol Metab 97: 1298 ATA low risk patients, followed for a median of 10.3 years: no significant effect of RAI ablation on overall or disease-free survival, using respective multivariate analysis.

•  National Thyroid Cancer Treatment Cooperative Study Group (NTCTCSG): overall disease-specific and disease-free survival not improved by RAI treatment in Stage I and II patients by multivariate analyses.

•  Lamartina L, et al. J Clin Endocrinol Metab 2015: systematic review of the literature supported the findings o fno effect of RAI on survival and recurrence in low risk patients.

•  The presence of micro-lymph node metastases does not change this scenario



Question 4.


RAI ablation is not indicated in classic PTC that have: •  T1b/T2 (1 – 4 cm) cN0 disease •  Small volume N1a disease (fewer than 3 – 5

metastatic lymph nodes with < 2 – 5 mm of focus of cancer)

•  Particularly if postoperative Tg < 1.0 ng/mL in absence of interfering anti-Tg Ab.


Indications for RAI



Indica<onsforRAI




Question 4.


Let’s go back to Clinical case #1: Emanuela


•  Emanuela, after considering the two possible surgical options, asked for a total thyroidectomy

•  Total thyroidectomy plus right central neck dissection was performed

•  Histologic report: «Right lobe PTC (classic variant), 7 mm in diameter. No other neoplastic foci either in the right or in the left lobe.

•  2 out of 8 lymph nodes of the central comparment shows micrometastatic involvement». pT1N1a.

Let’s go back to Clinical case 1. Emanuela’s surgical choice


In case of RAI ablation, what about the dose and patient preparation?

Question n.5


In patients with ATA low risk and ATA intermediate risk DTC without extensive LN involvement (ie. T1-T3, N0/Nx/N1a, M0), preparation with rhTSH stimulation is an acceptable alternative to thyroid hormone withdrawal for achieving remnant ablation.

(Strong recommendation, Moderate-quality evidence)


•  If radioactive iodine remnant ablation is performed after total thyroidectomy for ATA low risk thyroid cancer or intermediate risk disease with lower risk features (ie. low volume central neck nodal metastases with no other known gross residual disease nor any other adverse features), a low administered dose activity of approximately of 30 mCi (1.11 GBq) is generally favored over higher administered dose activities.

(Strong recommendation, High-quality evidence)


HYLO TRIAL 468 patients

FRENCH TRIAL 700 patients

……recently the results of two large trials have been published in the NEJM…. comparing 30 mCi with 100 mCi and

……hypothyroidism with rhTSH

Question 5: RAI dose and patient preparation


0

,2

,4

,6

,8

1

Cum

. Sur

viva

l

0 3 5 8 10 13 15 18 20Time

Cum. Survival (LOW DOSE)Cum. Survival (HIGH DOSE)

Logrank test: p=0.59

The recurrence free-survival at 5 and 10 years was 96.5% and 90% in patients treated with low activity and 98% and 92.7% in patients treated with high activity

of 131I. (Mean follow-up: 5.0±3.4 anni )

Recurrences in 366 DTC patients according to the 131I activity administrated

University of Siena

DFS

rate

years


FRENCH TRIAL: Hypo vs rhTSH

0

20

40

60

80

100

30 mCi 100 mCi

HYPORhTSH

%

92% 93% 89% 89%

p=NS

Catargi B et al, ETA September 2011



Question 5.


•  rhTSH is the recommended method of preparation for RRA in patients who have the following characteristics: •  pT1 to T3, pN0 •  NX or N1, and M0 and R0



Activity of 131I

•  Patients with pT1-2, N0 with no microscopic residual disease should receive 1100 MBq

•  Patients with pT3 and/or N1 disease, the final choice of 131I activity should be decided by the MDT on an individual case basis taking all prognostic factors into consideration.




Question 5


Grazie per l’attenzione!

carcinoma diﬀerenziato tiroideo le linee guida … diﬀerenziato tiroideo le linee guida nella...

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