Flow charts with recommendations for Management of medullary carcinoma of thyroid based on latest NCCN guidelines and ATA guidelines. Recent Advances in management included.

1. 1
MANAGEMENT OF
MEDULLARYCARCINOMA OF THYROID
DR. SANA ABOOSALIH

2. 2
Clinical Presentation & Work Up
Medullary thyroid carcinoma
on FNA
Medullary thyroid carcinoma diagnosed
after initial thyroid surgery
• Basal serum calcitonin level
• CEA
• Pheochromocytoma screening
• Serum calcium
• Screen for germline RET proto‐oncogene mutations
• Thyroid and neck ultrasound (including central and
lateral compartments)
• Consider evaluation of vocal cord mobility
• Additional cross‐sectional imaging (based on high
burden of disease, calcitonin g >400 pg/mL, or
elevated CEA levels)
• CECT neck/chest and liver MRI or 3 phase CT of
liver
• Ga‐68 DOTATATE PET CT/ Bone scan/ Skeletal
MRI
• Basal serum calcitonin level
• CEA
• Screen for germline RET proto‐oncogene mutations
• Central and lateral neck compartments ultrasound,
if not previously done

3. 3
Revised ATA MTC Risk Levels and Pediatric Recommendations

4. 4
If a Germline mutation of
RET proto‐ oncogene +
Multiple endocrine
neoplasia (MEN2B) (RET
mutations)
CEA
Pheochromocytoma
screening
Central and lateral neck
compartments ultrasound, if not
previously done
CECT neck
•Basal serum
calcitonin level
MEN2A/Familial medullary
thyroid carcinoma (FMTC) (RET
mutations)
CEA
Pheochromocytoma
screening
Sr Ca + PTH
Central and lateral neck
compartments ultrasound, if not
previously done
CECT neck
Basal serum
calcitonin level

5. 5
Evidence of pheochromocytoma
should be evaluated and treated
appropriately before proceeding to
the management of MTC

6. 6
Work Up for Germline mutation
of RET proto‐ oncogene
1. Germline mutation should prompt specific mutation testing in subsequent family members and genetic counseling.
2. The timing of prophylactic thyroidectomy generally depends on the aggressiveness of the inherited RET mutation.
3. Codon M918T mutations are considered highest risk and codon 634 and A883F mutations are considered high risk, with
MTC usually presenting at a younger age.
4. RET mutations associated with MEN2A or FMTC are generally moderate risk.
5. Prophylactic thyroidectomy may be delayed in patients with less high‐risk RET mutations, provided
• the annual basal calcitonin measurement is normal,
• the annual ultrasound is unremarkable,
• there is no history of aggressive MTC in the family,
• and the family is in agreement.
6. Screening for pheochromocytoma (MEN2A and MEN2B) and hyperparathyroidism (MEN2A) should be performed annually.
7. Parathyroid imaging may include USG / sestamibi scan with SPECT / 4D‐CT

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PRIMARY TREATMENTfor MTC DIAGNOSED BY
FNA
≥1.0 cm in diameter or
bilateral thyroid disease
<1.0 cm in diameter and
unilateral thyroid disease
• Total thyroidectomy with bilateral central neck dissection
(level VI)
• Therapeutic ipsilateral/ bilateral modified neck dissection for
clinically or radiologically identifiable disease (levels II–V)
• Consider prophylactic ipsilateral modified neck dissection for
high‐volume or gross disease in the adjacent central neck
• Consider therapeutic EBRT/IMRT for grossly
incomplete tumor resection when additional
attempts at surgical resection have been ruled out
• Adjuvant EBRT/IMRT is rarely recommended
• Postoperative administration of levothyroxine to normalize TSH
• Total thyroidectomy and consider neck
dissection (level VI)
> 4cm Total thyroidectomy + bilateral central neck
dissection + ipsilateral modified neck dissection
(levels II–V)

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PRIMARY TREATMENTfor MTC diagnosed
after initial thyroid surgery
Germline RET mutation identified Germline RET mutation not identified
Multiple endocrine neoplasia
(MEN2B) (RET mutations)
MEN2A/Familial MTC
(RET mutations)
• Total thyroidectomy during the
first year of life or at diagnosis.
• Therapeutic neck dissection as
indicated; consider prophylactic
bilateral central neck dissection
(level VI)
• Consider more extensive node
dissection (levels II–V) if tumor(s)
>0.5 cm in diameter
• Postoperative administration of
levothyroxine to normalize TSH
Measure serum calcium
± PTH
No primary hyperparathyroidism
Primary hyperparathyroidism
• Total thyroidectomy by age 5, or when mutation
identified(if mutation identified at older age)
• Therapeutic ipsilateral or bilateral central neck dissection (level VI) if
elevated calcitonin or CEA test or ultrasound identified thyroid or
nodal abnormality
• Consider prophylactic ipsilateral modified neck dissection if there is
high‐volume or gross disease in the adjacent central neck
• Consider more extensive lymph node dissection (levels II–V) if
tumor(s) >1.0 cm or central node(s) positive
• Postoperative administration of levothyroxine to normalize TSH
During primary operative procedure
and parathyroid exploration:
• If single adenoma – excise
• If multiglandular disease --
autotransplant or leave the
• equivalent mass of one normal
parathyroid gland
• Consider cryopreservation of
parathyroid tissue
If initial thyroid surgery was less than a total thyroidectomy,
additional surgical intervention may not be necessary unless
there is a positive germline RET mutation or radiographic
evidence of disease (ie. biopsy‐proven residual neck disease).

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MANAGEMENT 2–3 MONTHS POSTOPERATIVE
• Basal calcitonin
• CEA
Detectable basal calcitonin or
Elevated CEA
Basal calcitonin undetectable and
CEA within reference range
• Neck ultrasound
• If calcitonin ≥150 pg/mL, CT with contrast
of neck, liver, and chest.
• Consider bone scan and MRI of axial
skeleton in patients with very elevated
calcitonin levels
Imaging positive
or symptomatic disease
Imaging negative and asymptomatic
DISEASE MONITORING
Serum calcitonin, CEA every 6–12 mo
Additional studies or more frequent testing
based on calcitonin/CEA doubling time
FDG PET/CT or Ga‐68 DOTATATE or MRI with
contrast of the neck, chest, abdomen with
liver protocol
No additional imaging required if calcitonin
and CEA stable
DISEASE MONITORING
Annual serum calcitonin, CEA
Consider central and lateral
neck compartments ultrasound
Additional studies or more
frequent testing if significantly
rising calcitonin or CEA
No additional imaging required
if calcitonin and CEA stable
For MEN2B or MEN2A, annual
biochemical screenings for
pheochromocytoma and
hyperparathyroidism (MEN2A)
MANAGEMENT OF
RECURRENT OR
PERSISTENT DISEASE

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DURING DISEASE MONITORING:
WHEN NEGATIVE RESULT (no elevated calcitonin, CEA, negative imaging)
• Continue disease monitoring
or
Consider cervical reoperation, if primary surgery incomplete (Detectable basal calcitonin )
WHEN POSITIVE RESULT
(Imaging positive or symptomatic disease, increase markers)
MANAGEMENT OF RECURRENT OR PERSISTENT DISEASE

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RECURRENT OR PERSISTENT DISEASE –
LOCOREGIONAL DISEASE
• Surgical resection is the preferred treatment modality
• EBRT/IMRT can be considered for unresectable disease
• or, less commonly, after surgical resection
• Consider systemic therapy for unresectable disease that is symptomatic or progressing by RECIST criteria
Preferred Regimens
Vandetanib (category 1)
Cabozantinib (category 1)
Selpercatinib (RET mutation‐positive)
Pralsetinib (RET mutation‐positive)
• Useful in Certain Circumstances -- Pembrolizumab (TMB‐H [≥10 mut/Mb]
• Disease monitoring

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Asymptomatic disease
RECURRENT OR PERSISTENT DISEASE –
DISTANT METASTASIS
• Disease monitoring
• Consider resection (if possible), ablation (eg, RFA, embolization, other regional therapy)
• Systemic therapy if not resectable and progressing by RECIST criteria
 Preferred Regimens
Vandetanibs
Cabozantinib
Selpercatinib (RET mutation‐positive)
Pralsetinib (RET mutation‐positive)
 Useful in Certain Circumstances -- Pembrolizumab (TMB‐H [≥10 mut/Mb])
• Systemic therapy or clinical trial
Preferred Regimens
Vandetanib (category 1)
Cabozantinib (category 1)
Selpercatinib (RET mutation‐positive)
Pralsetinib (RET mutation‐positive)
Clinical benefit can be seen in
both sporadic and familial MTC
SYMPTOMATIC / PROGRESSIVE DISEASE continued…

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Symptomatic disease
or progression
• Other Recommended Regimens
Consider other small‐molecule kinase inhibitors
Dacarbazine (DTIC)‐based chemotherapy
Useful in Certain Circumstances t -- Pembrolizumab (TMB‐H [≥10 mut/Mb]
• EBRT/IMRT for local symptoms
• Consider intravenous bisphosphonate or denosumab therapy for bone metastases
• Consider palliative resection, ablation (eg, RFA, embolization, other regional therapy), or other
regional treatment
• Best supportive care

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RECENT ADVANCES - Peptide Receptor Radionuclide Therapy
• Somatostatin receptor (SSR) expressions in MTC cells have been reported invitro and in vivo.
• This finding provides the basis for peptide receptor radionuclide therapy (PRRT) with radiolabelled
somatostatin analogues (SSAs)
• The use of a concomitant radio sensitising agent, like low-dose oral capecitabine, is more beneficial.
• LUTATHERA – lutetium 177-Dotatate.

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THANK YOU