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BALKAN MCO 2011 - A. Celebic - Thyroid cancer
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BALKAN MCO 2011 - A. Celebic - Thyroid cancer

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  • In this sense, the ETA…
  • Evaluation starts with clinical history and physical examination of the thyroid and neck.After that e perform US and Laboratory tests. Depending on findings, we can proceed to follow up , Thyroid scan, FNAC and than again to: follow-up or to surgery…

BALKAN MCO 2011 - A. Celebic - Thyroid cancer BALKAN MCO 2011 - A. Celebic - Thyroid cancer Presentation Transcript

  • ESO Masterclass in Clinical Oncology Dubrovnik 2011 THYROID CANCER Dr Aleksandar CELEBIC, MD, PhD - Clinical Center of Montenegro, Podgorica, Montenegro - Institute Gustave Roussy, Villejuif, France
  • INTRODUCTION
    • Thyroid cancer is rare among human malignancies - accounts for approx. 1% of all cancers
    • But: Most common endocrine malignancy (95%)
    • Present in about 5% of thyroid nodules
    • The incidence of thyroid cancer, mainly differentiated, is one of the most rapidly increasing human cancers
    • In Women 3 times more frequent than in men
    • Peak incidence 30-40s
  • Classification & Incidence of Thyroid cancer
    • Follicular cell origin
    • * Differentiated
    • - Papillary……………………………………. 80%
    • - Follicular…………………………………… 10%
    • - Hurthle cell……………………………….. 3-5%
    • * Undifferentiated
    • - Anaplastic…………………………………. 1-2%
    • Parafollicular cell origin
    • - Medullary………………………………….. 5%
  • Papillary Carcinoma
    • Accounts for 90% radiation induced cancers
    • Classified as microcarcinoma, intrathyroidal and extrathyroidal
    • Multicentric in 30-50% of tumors
    • Spreads by lymphatics with propagation for mid- and lower-anterior cervical chain (level VI: pretracheal and para-tracheal LN)
    • 20-50% patients have involvement of cervical LN
  • Follicular Carcinoma
    • Accounts only 10% of all thyroid cancers, although more prevalent in regions with iodine deficiency
    • Differentiated from follicular adenomas by the presence of vascular or capsular invasion
    • Cannot reliably diagnose based on FNA
    • Uncommon to have multicentric disease
    • Hematogenous spread
    • Shows tendency to metastasize: bone, lung
  • Hurthle Cell Carcinoma
    • often considered a variant of follicular cell carcinoma
    • High tendency to spread to cervical lymph nodes and high incidence of distant metastasis
    • Less than 10% of Hurthle cell carcinomas take up radioiodine
    • High tumor recurrence rate
    • High mortality rate - 30% at 10 yrs
  • Anaplastic Carcinoma
    • Rare: 1-2% of all TCs
    • Arise within differentiated cancers
    • Typically: pts > 60 yrs old with rapidly expanding neck mass
    • Surgery plays limited role because given advanced stage at Dx
    • RT and Chemoth. have not demonstrated any significant improvement in survival
    • Median survival 4-6 months
  • Medullary Thyroid Carcinoma
    • Originates from the parafollicular C-cells
    • Common elevation in calcitonin and CEA (50%)
    • 80% have sporadic MTC (unifocal)
    • 75% patients have LN metastasis at time of dx, 20% distant metastasis
  • Medullary Thyroid Carcinoma
    • Associated with genetic syndromes
    • MEN IIA:
    • - MTC (100%), pheo (40%), hyperparathyreoidism (35%)
    • - AD inheritance
    • - Missence mutation of extracellular cysteine domain
    • - Surgery recommended before 6 yrs of age
    • MEN IIB:
    • - MTC (100%), pheo (50%), mucosal ganglioneuromas (100%)
    • - AD inheritance
    • - Missence mutation of thyrosin kinase domain
    • - Surgery recommended in infancy
    • Familial MTC
  • FACTEURS PRONOSTIQUES
    • Age
    • Histologie
    • Masse tumorale:
    • - taille
    • - envahissement en dehors de la capsule thyroïdienne
    • - métastases ganglionnaires
    • - métastases à distance
    • Autres
  • Guidelines and consensus reports
    • There was a need for uniform diagnostic and treatment strategies for thyroid nodules and differentiated thyroid cancer (DTC) - since the disease requires a multidisciplinary approach , including physicians in endocrinology, internal medicine, nuclear medicine, oncology, surgery and even general practice
    • Following the spirit of concrete cultural and scientific integration among the countries participating in the new reality of the European Union, the European Thyroid Association (ETA) has endorsed the implementation of its own guidelines/recommendations/consensus reports for the management of thyroid nodules and DTC
    • ATA Guidelines: 80 recommendations on Dg, Th and follow-up (Cooper D et al., Thyroid, vol 19, Number 11, 2009)
  • ACTIONS - European Thyroid Association
    • 25 countries appointed a total of 50 experts who created a taskforce with two coordinators for the development of the consensus
    • They identified the most relevant diagnostic and therapeutic issues:
  • pre-surgical evaluation of thyroid nodules; surgical treatment; tumor-node-metastasis (TNM) and other prognostic systems; postsurgical administration of radioiodine; follow-up: role of diagnostic whole body scan (WBS), role of thyroglobulin (Tg), anti-Tg antibodies (AbTg) and neck US; protocols for early and long-term follow-up; treatment of local and regional recurrences and of distant metastases
  • Thyroid nodules
    • evaluation
    • Thyroid nodules do not reflect a single disease but are the clinical manifestation of a wide spectrum of different thyroid diseases
    • Thyroid nodules may be solitary or multiple
    • Among multinodular goiters, one nodule may become clinically dominant in terms of growth, dimension, and functional characteristic
    • The risk of malignancy is similar among hypofunctioning solitary nodules and multinodular goiter
    • The aim of the diagnostic approach to thyroid nodules is the differential diagnosis between benign and malignant nodules and, in the event of malignancy, the selection of an appropriate surgical procedure (Fig. 1 )
  • Copyright ©2010 European Society of Endocrinology Eur J Endocrinol. 2006 Jun;154(6):787-803 Figure 1 Flow chart for the diagnostic evaluation of thyroid nodule(s) ‏
  • Thyroid nodules
    • thyroid and neck ultrasonography
    • Thyroid US is the most accurate imaging technique for the detection of thyroid nodules
    • US can accurately differentiate cystic from solid lesion, identify the features, the number, the location and the size of nodules
    • Ultrasonographic features suggestive of malignant thyroid nodules are the following: hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, intranodular hypervascularity and regional lymphadenopathy
    • US is also a guide to FNAC
  • Thyroid nodules
    • thyroid scintigraphy
    • Determines function of the nodule: ‘cold’ nodules are those that don’t take up iodine 123, ‘hot’ ones are the opposite
    • Cancer can not be ruled out based on scans , with 4% of ‘hot’ nodules being malignant
    • May, however, be useful with ‘indeterminate’ findings
  • Thyroid nodules
    • fine needle aspiration cytology
    • First intervention in evaluation of a nodule
    • Inexpensive, easy, few complications
    • Need a good cytopathologist
    • Four types of results: benign, malignant, indeterminate, non-diagnostic
    • 69% benign, 4% malignant, 10% indeterminate, 17% non-diagnostic
    • Sensitivity 83%, Specificity 92%
    • False positive 2.9%, false negative 5.2%
  • Thyroid nodules
    • fine needle aspiration cytology
    • FNAC is the gold standard for differential diagnosis, although there are limitations: inadequate samples and follicular neoplasia
    • FNAC can diagnose papillary and medullary cancers
    • In the event of inadequate (non-diagnostic) samples, FNAC is repeated
    • If malignant = go to operation
    • If indeterminate or suspicious = go to operation
    • If benign = stop and follow
  • Thyroid nodules
    • laboratory evaluation
    • Measurement of serum TSH is indicated at the first visit of the patient to rule out the presence of underlying thyroid disorders (hypo- and hyperthyroidism), but does not rule out malignancy; if low = radioisotope study; if normal or high, then proceed to US examination
    • Measurements of thyroid autoantibodies are useful for the detection of autoimmune thyroiditis but their contribution to the differential diagnosis of thyroid nodules is poor
    • Measurement of serum Tg has no role in the diagnostic evaluation of thyroid nodules, since its concentration is correlated with the size rather than with the nature of the nodule or of the thyroid gland
    • Calcitonin , for monitoring in medullary cancers
  • Differentiated thyroid cancer
    • preoperative staging
    • surgery must be preceded by an ultrasonographic evaluation of the lymph node chains because of the high rate of cervical LN mets in papillary cancer
    • computed tomography (CT), magnetic resonance (MR) and positron emission tomography (PET) scan, are not indicated as routine procedures , but may be required in selected patients with clinical evidence of local extension or of distant metastases
  • Surgical treatment
    • Surgery for thyroid cancer should be performed by experienced surgeons involved in multidisciplinary teams , trained specifically in thyroid cancer surgery and operating on a large number of thyroid cancer patients annually, including both primary as well as re-operative cases.
    • The standard surgical treatment for thyroid cancer is total (or near-total) thyroidectomy
    • (recommendation A European consensus)
    • This procedure decreases the risk of local recurrence
    • Moreover, it facilitates postsurgical radioiodine ablation and adequate follow-up
    • However, the ATA Guidelines Taskforce ‘allow’ loboisthmectomy for cases with solitary well differentiated thyroid cancer less than 1 cm in diameter with no evidence for nodal or distant metastases, and no history of previous radiation exposure
    • ATA: Compartment-oriented
    • LND should be performed in
    • cases of preoperative suspected
    • and/or intraoperatively proven
    • lymph node metastases -
    • central compartment
    • (level VI or more extensive LND)
    • ETA: Central compartment LND
    • should be performed routinely
    • in cases with papillary and
    • Hurthle cell cacinoma
    • (rcommend. B - without
    • consensus)
    • Those gross cervical mets should be removed ‘en bloc’ with a dissection in the compartment in which they reside
    • Surgical complications:
    • 1. permanent unilateral recurrent laryngeal nerve paralysis (RLNP)
    • 2. hypoparathyroidism
  • Post-operative radioiodine administration (thyroid remnant ablation)
    • Thyroid ablation refers to the postsurgical administration of 131I, whose aim is to destroy any thyroid residue in the thyroid bed
    • Its use is based on the following assumptions:
    • 131I treatment of residual postoperative microscopic tumor foci may decrease the recurrence rate and possibly the mortality rate
    • - 131I ablation of residual normal thyroid tissue facilitates the early detection of recurrence based on serum Tg measurement and eventually on 131I WBS
    • - A high activity of 131I permits a highly sensitive post-therapy WBS, 2–5 days after its administration, and this may reveal previously undiagnosed tumors
  • Post-operative radioiodine administration (thyroid remnant ablation)
    • To whom should it be offered?
    • Staged III and IV disease
    • Stage II disease in pts under age 45
    • Selected pts with Stage I:
    • Multifocal disease
    • Nodal metastasis
    • Extrathyroidal extension
    • Vascular invasion
    • Aggressive histology
  • Pathological and clinical staging after initial treatment
    • Conventionally, staging of DTC is based on the pathological assessment with the addition of information derived from the postsurgical 131I WBS , if this is performed within 3 months of thyroidectomy
    • Postoperative staging allows risk stratification of individual patients , which will dictate the frequency and type of follow-up
  • TNM classification
    • T: tumeur thyroïdienne
    • T1< 2 cm
    • T2:>2-4cm
    • T3:>4cm et/ou extension
    • extrathyroïdienne minime
    • T4: extension extrathyroïdienne
    • N: métastases ganglionnaires
    • N0, absence; N1, présence
    • • M : métastases à distance.
    • M0, absence; M1, présence
  • Les stades
    • < 45 ans:
    • Stade 1: M0
    • Stade 2: M1
    • >= 45 ans
    • Stade 1:T1
    • Stade 2:T2-T3
    • Stade 3:T4 ou N1
    • Stade 4:M1
    • In accordance with AJCC staging system, the panel agreed to group patients into three risk categories at the time of initial treatment:
    • very low risk : unifocal T1 (1 cm) N0M0 and no extension beyond the thyroid capsule
    • low risk: T1 (>1 cm) N0M0 or T2N0M0 or multifocal T1N0M0
    • high risk: any T3 and T4 or any T, N1 or any M1
  • Thyrotropin-suppressive therapy
    • The role of TSH-suppressive therapy after initial treatment is twofold:
    • the first aim is to correct the hypothyroidism using a dosage appropriate to achieve normal blood levels of thyroid hormone
    • the second aim is to inhibit the TSH-dependent growth of residual cancer cells by decreasing the serum TSH level to 0.1 mU/l
  • Thyrotropin-suppressive therapy
    • In patients considered in complete remission at any time during follow-up, there is no need to suppress endogenous TSH and thus therapy may be shifted from suppressive to replacement
    • LT4 is the drug of choice
    • When the optimal dose of LT4 has been achieved, it should not be modified and serum FT4, FT3 and TSH is monitored every 6-12 months
    • TSH-suppressive therapy (serum TSH 0.1 mU/l) is mandatory in patients with evidence of persistent disease
    • In high-risk patients who have achieved remission after treatment, suppressive therapy is advised for 3–5 years
  • Recommendations for follow-up 6-12 months after thyroid ablation
    • After total thyroid ablation by surgery and radioiodine, the Tg level should be undetectable and any detectable level should alert the clinician
    • However, serum Tg may remain detectable for some months after surgery or radioiodine treatment. Thus, serum Tg should not be measured less than 3 months after initial treatment
  • Copyright ©2010 European Society of Endocrinology Eur J Endocrinol. 2006 Jun;154(6):787-803 Figure 2 Flow chart for the follow-up after initial treatment (surgery and radioiodine ablation)‏
  • Recommendations for follow-up 6-12 months after thyroid ablation
    • Thyroid cancers recurs in 20-40% patients, most commonly within the first 2 years
    • At 6-12 months, disease status is assessed by physical examination , neck US , and serum Tg determination obtained 3 days after the injection of rhTSH stimulation
    • Whole Body Scan may be useful in intermediate and high-risk patients 6-12 months after ablation
  • Long-term follow-up
    • Follow-up comprises serum TSH and Tg determinations on LT4 treatment together with a physical examination , on a yearly basis
    • Neck US is performed either routinely or only in patients with suspicious clinical findings
    • Follow-up should be continued throughout life
  • Management of patients with recurrent or metastatic disease
    • Local and regional recurrence  
    • Treatment is based on the combination of surgery and 131I , in those with 131I uptake
    • When complete surgical excision is not possible, external beam radiotherapy may be indicated if there is no significant radioiodine uptake within the tumor
  • Distant metastases
    • Lung metastases:   In the case of 131I uptake, treatment consists of 131I administration
    • Bone metastasis: Surgery , 131I (if uptake), external beam RT as well as bisphosphonates, cement injection and embolization
  • Role of external beam radiotherapy
    • External beam RT to the neck is used infrequently
    • It is indicated as initial treatment or for recurrence of unresectable tumors or local invasion presumed to have macro- or microscopic residual disease, which does not concentrate 131I
    • For microscopic residual disease it should deliver a total dose of 50–60 Gy to the neck and upper mediastinum , in 25–30 sessions with five sessions per week
    • A boost of 5–10 Gy may then be given to any gross residual neoplastic focus .
  • Role of chemotherapy and experimental therapies
    • Cytotoxic chemotherapy has no role in routine management of papillary and follicular thyroid cancer
    • Its use is restricted to patients with progressive disease uncontrolled by surgery , 131I or other treatment modalities
    • Response is poor , at best 10-20% with single-agent doxorubicin or the combination of doxorubicin-cisplatin
    • Molecular targeted therapies and anti-angiogenic agents are being studied in prospective controlled trials and may represent hope for such patients
    • Thank you!