Post-Operative Management and Follow Up of Differentiated Thyroid Carcinoma
1. üPOST OPERATIVE MANAGEMENT & FOLLOW UP
üCOMPLICATIONS OF THYROID SURGERY
üPROGNOSIS
üSCREENING
üSUMMARY & RECOMMENDATIONS
THYROID CARCINOMA.04
PRESENTER: JASHANPREET
MBBS BATCH 2K17
MODERATOR: DR. ZAHID IQBAL MIR
MBBS, MS, DNB
2.
3. POST-OPERATIVE MANAGEMENT OF DTC:
RADIOIODINETHERAPY: 131I can be given in order to
deliver tumouricidal doses of radioactivity directly to thyroid
tissue.
•No value in patients whose thyroid cancers do not
concentrate iodide (ie,MTC,ATC,Lymphoma).
•In order to effectively drive the radioiodine into cells,high
levels ofTSH are required.
4. GOALS OF RAI THERAPY
ABLATION OF REMNANT
-Thyroid tissue to
facilitate detection
of later disease
recurrence by
imaging andTg
assay
ADJUVANT THERAPY
- targeting occult
metastatic disease
TREATMENT OF KNOWN
DISEASE
-destruction of
clinically apparent
macroscopic disease
not amenable to
surgical therapy
5. HIGH LEVEL OFTSH ACHIEVED BY
ØThyroid hormone withdrawal:
üAfter thyroidectomy or cessation of T4 (levothyroxine) therapy,the patient's serumT4
must decline sufficiently to allow the serumTSH concentration to rise to above
25 to 30 mU/L.
üT4 therapy should be discontinued for approximately 6 weeks before
scanning with 131I.
üT3 during this time period.
üT3 has a shorter half-life thanT4,needs to be discontinued for 2 weeks to
allowTSH levels to rise before treatment.
6. Ø RecombinantTSH
ü rhTSH (0.9 mg) IM * 2days f/b administration of radioiodine on the day following the
second injection (ie,the third day).
ü SerumTg - 72 hours after the second rhTSH injection (the fifth day)
ü Whole body scan - 2-7 days after the radioiodine administration
LOW IODINE DIET
ü 7 to 10 days before and for 1-2 days after 131-I is administered.
OTHERS
ü Loop diuretics,mannitol with strict low iodine diets may increase uptake by tumor,
however,there may also be a concomitant increase in total body irradiation.
ü Lithium can prolong 131-I retention by thyroid tissue.
7. SCANNING DOSE
üPretreatment whole-body scanning – Low dose,orally
administered activities of 2 to 5 mCi (74 to 185 MBq) 131-I
should be used with whole-body imaging 48 to 72 hours later to
identify thyroid tissue and metastases.
üA“hot”spot in the neck - residual normal tissue in the thyroid bed.
8. RADIOIODINE DOSE (ACTIVITY)
üWhen the primary goal is:
§Remnant ablation:administered activities of 30 mCi (1.1 GBq) are typically
used.Higher doses (less than a total thyroidectomy).
§ Adjuvant treatment of subclinical micrometastatic disease: administered
activities of 75 to 150 mCi.
§Treatment of clinically apparent residual or metastatic thyroid cancer:
administered activities of 100 to 200 mCi are typically used.
MAX: 200 mCi (Cumulative dose of 1000 to 1500 mCi)
9. MONITORING AFTER RADIOIODINE THERAPY
üPOST-TREATMENT SCANNING
Whole body scanning 2-8 days after radioiodine treatment.
üREPEAT SCANNING ANDTREATMENT
follow-up radioactive scans - persistent/recurrent disease.
11. ØTHYROID HORMONE:
For high risk patients:
üCurrent guidelines advise maintaining initialTSH levels <0.1 Mu/Ml.
For low risk patients:
üthyroxine replacement at physiological levels.
üFor low-risk patients (with or without remnant ablation) with undetectable serumTg levels,TSH
levels can be maintained at the lower end of the reference range (0.5–2 mU/L).
For intermediate risk patients:
ü0.1 to 0.5 mU/mL
The risk of tumor recurrence must be balanced with the side effects associated with prolongedTSH
suppression,including osteopenia and cardiac problems,particularly in older patients.
12. FOLLOW-UP OF PATIENTS WITH DTC
ØTHYROGLOBULIN MEASUREMENT:
ü Tg and anti-Tg antibody levels should be measured initially at 6 to 12
month intervals and more frequently in patients with high risk tumors.
Patients are considered to have an excellent response to treatment if
suppressed Tg is <0.2 ng/mL and stimulated Tg is <1.0 ng/Ml with
negative imaging.In these patients,Tg levels can be followed every 12 to 24
months while on thyroid hormone as their risk of recurrence is low (1–4%).
13. Additional investigations are needed in:
• Patients with structurally or biochemically incomplete response
(negative imaging but suppressedTg ≥1 ng/ ml or stimulatedTg ≥ 10ng/ml or
rising anti-Tg levels)
• Patients with indeterminate responses (nonspecific imaging findings,
suppressedTg detectable but <1 ng/ml L,and stimulatedTg detectable but
<10ng/ml or stable or declining anti-Tg levels).
14. ØWHOLE BODY SCANS:
üDiagnostic whole-body scans 6 to 12 months after remnant ablation
üOther scenarios for follow-up scans include
•patients with abnormal uptake outside the thyroid bed on post-therapy scan
•Those with poorly informative post-ablation scans (e.g.,due to high thyroid
bed uptake)
•patients withTg antibodies.
15. ØCERVICAL USG
üTo evaluate the thyroid bed and central and lateral cervical nodal compartments at 6 and
12 months after thyroidectomy and then annually for at least 3 to 5 years,
depending on the patient’s risk for recurrent disease andTg status.
ü Suspicious nodes ≥8 to 10 mm on the smallest diameter measurement should be
biopsied for cytology as well asTg measurement in the aspirate washout.
ØFDG PET & PET CT
üLocalize recurrent or persistent thyroid cancer in patients who have Tg-positive,RAI scan
–negative disease.
üInitial staging of patients with poorly differentiated thyroid carcinomas or Hürthle cell
tumors,particularly in patients with other evidence of disease on imaging orTg levels.
16. DTC- REFRACTORY TO STANDARD TREATMENT
ØCANDIDATES FOR SYSTEMICTHERAPY:
üUnresponsive metastatic tumors of at least 1 to 2 cm in diameter and growing by
at least 20 % per year
üSymptoms related to multiple metastatic foci that cannot be alleviated with
localized treatment such as surgery or EBRT
§Multitargeted kinase inhibitor - lenvatinib ,Sorafenib
17. üVandetanib -oral inhibitor that targetsVEGFR,RET/PTC,EGFR
Contraindications to aaMKI:
üMajor surgery within 28 days,active bleeding,untreated hemorrhagic brain metastases,encasement by
tumor of major arteries such as the carotid,or arterial thromboembolic event within the last 6 to 12
months.
§Mutation-specific kinase inhibitor
üTRK Inhibition- Larotrectinib ,entrectinib
üRET inhibition- Selpercatinib,pralsetinib
üBRAF inhibition -Vemurafenib and dabrafenib
üPI3K inhibition - everolimus
18. POST-OPERATIVE MANAGEMENT: MEDULLARY
CARCINOMA
üMonitor for postoperative complications
•Hypoparathyroidism
•injury to either the recurrent or superior laryngeal nerves.
üThyroxine therapy —levothyroxine (T4) - immediately after surgery -
1.6 mcg/kg of body weight.
Suppression of serum TSH concentrations is not indicated in patients with
medullary thyroid cancer (MTC), because C cells are not TSH responsive. Similarly,
adjuvant therapy with radioiodine is contraindicated because the tumor cells do
not concentrate iodine
19. üAssessment of tumor
samples for somatic
mutations
•RET, HRAS, KRAS, or, rarely,
NRAS
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20. FOLLOWUP : MEDULLARY CARCINOMA
Serum calcitonin and CEA measurement:
ü2-3 months after surgery to detect the presence of residual disease.
• normal serum CEA and undetectable serum calcitonin - biochemically cured and have the best
prognosis.
• High basal serum calcitonin value three or more months after surgery - residual disease.
Calcitonin values that are detectable
but less than 150 pg/mL
Ø persistent locoregional disease in the neck.
ü Neck ultrasound +/- additional cross-
sectional imaging (CT or MRI of the neck)
should be performed
Patients with postoperative calcitonin
levels that are ≥150 pg/mL
ü Neck ultrasound and additional imaging
(CT or MRI of neck,chest,and abdomen;
bone scan or bone MRI)
Ø possible distant metastases.
21. POST-OPERATIVE MANAGEMENT AND FOLLOWUP:
ANAPLASTIC CARCINOMA
üMost aggressive - few patients surviving 6 months beyond diagnosis.
üPatients who respond to initial management (M0 disease) require surveillance for
recurrence.
üNo known role for adjuvant therapy.
IMAGING:
CT at 4 weeks and a PET/CT scan at 3 months after the completion of chemoradiation
therapy.
•Thereafter,CECT neck,chest,and abdomen (including adrenal glands) every 1-3
months for the first 24 months and then less frequently (every 4-6 months) thereafter.
22. THYROID HORMONE REPLACEMENT:
T4- 1.6 mcg/kg of body weight immediately after surgery.
vThe goal ofT4 therapy should be to restore and maintain
euthyroidism
vsuppression of serumTSH concentrations to less than normal is not
indicated,unless for treatment of coexisting differentiated thyroid
cancer.
23. RESPONSE TO INITIAL THERAPY CATEGORIES
ØExcellent response: No clinical, biochemical, or structural evidence of
disease (1%–4% risk of recurrence)
ØBiochemical incomplete response: AbnormalTg or rising anti-Tg
antibody levels in the absence of localizable disease
ØStructural incomplete response: Persistent or newly identified
locoregional or distant metastases
ØIndeterminate response: Non specific biochemical or structural findings
that cannot be confidently classified as either benign or malignant, including
patients with stable or declining antiTg antibody levels without definitive
structural evidence of disease
The ATA guidelines - system that dynamically changes the initial risk estimates based on the clinical course of
disease and response to therapy
24.
25. 1.HYPOCALCEMIA AND HYPOPARATHYROIDISM:
•Hypoparathyroidism - Mc complication
•Temporary hypoparathyroidism - 5% to 15% (resolve within 6 months)
•Permanent hypoparathyroidism of 1% to 3%
Risk factors
ü Bilateral neck exploration
Extensive central neck dissec-
tion
ü Reoperative surgery
ü Graves disease
ü pediatric patients.
§ Evaluate the parathyroid tissue
intraoperatively.
§ If devascularized –
autotransplantation of 1 mm
fragments of saline chilled tissue into
pockets made in the
sternocleidomastoid muscle or the
brachioradialis muscle is
26. 2.BLEEDING - Postoperative hematomas
ü0.1% to 1.1% - thyroidectomy.
Risk factors
ü male sex
ü advanced age
ü bilateral operation
ü Graves disease
ü use of
anticoagulants.
Danger lies not in the effect of blood
loss on circulating blood volume,but rather
on the local compressive effect on the
trachea leading to rapid airway compromise.
C/F
Pain,oozing from the incision,
ecchymosis,firm swelling overlying
the resection bed and incision –
stridor with rapid airway collapse.
27. üMostly within the first 6 hours
ü20% of cases - between 6 and 24 hours
üVery few cases occur afterward.
Ø The key to management is early recognition and management.
•Signs of impending airway collapse – Incision should be opened immediately
wherever the patient may be.
•All three layers to the thyroidectomy bed - Skin,platysma,and strap
muscles opened
28. 3.NERVE INJURY
ØAll patients should undergo voice and vocal cord
assessment before thyroid surgery
ØRLN INJURY
üRates of temporary and permanent RLN injury
during thyroidectomy are in the 4% to 10% and
0.5% to 2% ranges,respectively
ü In pediatric population - up to fourfold higher
Risk factors for RLN
injury
ülow surgeon volume
ü reoperative thyroid surgery
üextensive surgery for
malignancy
üGraves disease
ülarge substernal goiter.
29. • Occur by severance,ligation,or
traction,
• The RLN is most vulnerable to injury
during the last 2 to 3 cm of course
•Can be damaged if the surgeon is not
alert to the possibility of nerve
branches and the presence of
non recurrent nerve,particularly
on the right side.
30. UNILATERAL INJURY BILATERAL INJURY
§ paralyzed vocal cord with loss of
movement from the midline.
§ new onset hoarseness,changes in
vocal pitch,or noisy breathing.
§ Airway obstruction - emergency
tracheostomy,or loss of voice.
§ If both cords in an abducted position -
ineffective cough and increased risk of
repeated RTI from aspiration.
MANAGEMENT:
ü Length of nerve is excised - anastomosis of the ansa cervicalis -
neurological input to the muscles of the larynx.
ü By avoiding denervation and related muscle atrophy, the vocal quality is
improved.
ü Permanent vocal cord paralysis - speech therapy
ü Voice quality is unacceptable - medialization procedure
31. ØSUPERIOR LARYNGEAL NERVE:
•External branch can run closely adherent
to the superior thyroid artery,and care
must be exercised during dissection in this
area.
•Injury causes voice changes,huskiness,
poor volume and projection,voice fatigue,
and inability to sing at higher ranges.
32. INTERNATIONAL NEURAL MONITORING STUDY GROUP
GUIDELINES 2018
1. Initial vagal nerve stimulation to confirm intact RLN
function and electrode position
2. Visual identification and direct stimulation of the RLN
during the course of thyroid lobectomy
3. Final reconfirmation of intact RLN function with vagal
nerve stimulation after completion of thyroid lobectomy.
33. ØOTHERS:
üSeromas - Aspiration
üWound cellulitis and infection and injury - to carotid
artery,jugular vein,and esophagus,are infrequent -Antibiotics.
üHypertrophic scar and keloid - Intradermal injections of
corticosteroids
üStich Granuloma - Absorbable sutures should be used
34. SCREENING FOR THYROID CANCER
ØMany thyroid cancers are now found much earlier than in the past.
ØTwo primary methods to screen for thyroid cancer:
1) neck palpation during a physical examination - palpable
nodules,
2) ultrasound neck - palpable and non-palpable nodules,
especially those smaller than 1 cm.
ØGenetic testing for these people when they are
young to see if they carry the gene changes linked to MTC.
35.
36. PROGNOSTIC SCORES
AGES(Mayo) AMES(Lahey) MACIS(Mayo)
(post-operative
score)
DAMES
(Karolinska)
GAMES(MSKCC)
Age Age Metastasis DNA Ploidy Grade
Grade Metastasis Age at
presentation
Age Age
Extrathyroidal
extension
Extrathyroidal
extension
Completeness of
original surgical
resection
Distant
Metastasis
Metastasis
Size Size Extrathyroidal
Invasion
Extrathyroidal
Extension
Extrathyroidal
extension
Size of original
lesion(in cm)
Size Size
37. § PTC - Excellent prognosis (>95% 10-year survival rate)
§ Among patients with small pulmonary metastases but no other
metastases outside of the neck,the 10-year survival rate is 30 to 50
percent;
§ Median survival of patients with brain metastases is one year.
§ Poorer prognosis in tall cell,insular,and hobnail variants.
38. §BRAFV600E mutation - aggressive tumor characteristics,including
extrathyroidal extension,older age at presentation,and lymph node and distant
metastases.
§TERT promoter mutations - poor disease specific and disease free survival.
§Tumor DNA aneuploidy,decreased CAMP response toTSH,increased
epidermal growth factor binding,presence of N-ras and gsp
mutations,overexpression of c-myc,and presence of p53 mutations also
have been associated with a worse prognosis.
39. §Follicular carcinoma - poor prognosis (if Age > 50 years at
presentation,tumor size >4 cm,higher tumor grade,marked
vascular invasion,extrathyroidal invasion,and distant metastases
at the time of diagnosis)
§Hürthle cell carcinoma - poorer prognosis
§Insular cancer (poorly differentiated follicular thyroid cancer
variant) - poor prognosis
40. §Medullary carcinoma - related to disease stage.
•10-year survival rate is 80% but decreases to 45% in
patients with lymph node involvement.
•Prognosis is the worst (survival of 35% at 10 years) in
patients with MEN2B.
•Calcitonin doubling times less than 6 to 12 months - poor
survival,doubling times >24 months - favorable prognosis.
41. §Anaplastic carcinoma - Most aggressive - few
patients surviving 6 months beyond diagnosis.
•Tumor size - important.
•worse prognosis - older age at diagnosis,male sex,
and dyspnea as a presenting symptom.