HIPOTIROIDISME PASCA

RADIOTERAPI UNTUK
KARSINOMA NASOFARING
DR. L.M. AKHIRUDDIN

Supervisor
Dr. dr. Nova AL Pieter, Sp. T.H.T.K.L(K) FICS
 INTRODUCTION

• Nasopharyngeal cancer (NPC): Malignancy of the

head and neck
• Main management: CHEMORADIATION
• Radiation: side effects (acute & late effect)
• Radiation-induced hypothyroidism (RIHT): the
most common late complication

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 PENDAHULUAN

• Kanker nasofaring (KNF): Keganasan pada kepala

leher
• Tatalaksana utama: KEMORADIASI
• Radiasi: efek samping (acute & late effect)
• Radiation-induced hypothyroidism (RIHT):
komplikasi lanjut tersering
N P C V S O T H ER H EA D A N D N E CK CA N CE R

I II
Definitive radiotherapy (RT) Intensity modulated
and/or chemotherapy: primary radiotherapy (IMRT):
treatment standard radiotherapy
technique

III IV
Pituitary gland: belongs to the Neck dissection surgery
radiation field involving the thyroid gland
is not performed  longer
survival

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K N F V S K A N K E R K EPA L A LE H E R L A I N

I II
Radioterapi definitive (RT) Radioterapi termodulasi
dan/atau kemoterapi: intensitas (IMRT): teknik
pengobatan utama radioterapi standar

III
Kelenjar hipofisis: termasuk
dalam lapangan radiasi
IV
Pembedahan diseksi leher
yang melibatkan kelenjar
tiroid tidak dilakukan 
kesintasan lebih lama

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 PENDAHULUAN

RIHT… RIHT INCIDENCE… LATE EFFECT…

Most common late effect on thyroid 23-53% in other head and neck Occurs within 2 years after radiation
after neck RT cancers and 14-54% in NPC

DELAYED DIAGNOSIS… RIHT INCREASED RISK OF …

Decreased quality of life & Ischemic heart disease, myxedema,
increased risk of life-threatening and birth defects
conditions

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 INTRODUCTION

RIHT… INSIDEN RIHT… EFEK SAMPING LAMBAT…

Efek akhir paling umum pada tiroid 23-53% pada kanker kepala leher Terjadi dalam 2 tahun pasca radiasi
pasca RT leher lain dan 14-54% pada KNF

PENUNDAAN DIAGNOSIS… RIHT MENINGKATKAN RISIKO…

Penurunan kualitas hidup & Penyakit jantung iskemik,
peningkatan risiko kondisi ancaman miksedema, dan defek kelahiran
jiwa

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INTRODUCTION
CURRENTLY…
There is no consensus on thyroid dose limits, even in
the Quantitative Analysis of Normal Tissue Effects in
the Clinic (QUANTEC)

PURPOSE OF STUDY…
Summarizing the pathophysiological changes of
the thyroid gland after radiation and thyroid
constraint recommendations from the literature as
well as predictive tools for predicting RIHT in
NPC

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PENDAHULUAN
SAAT INI…
Belum ada konsensus untuk batasan dosis kelenjar
tiroid, bahkan dalam Quantitative Analysis of Normal
Tissue Effects in the Clinic (QUANTEC)

TUJUAN STUDI…
Merangkum perubahan patofisiologi kelenjar
tiroid pasca radiasi dan rekomendasi constraint
tiroid dari beberapa literatur serta untuk
memprediksi RIHT pada KNF

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 PATH O PH Y S I O L O G Y O F T H E T H Y RO I D G LA N D

Thyroid: Produces and releases T3 & T4

I II III

Hypothalamus: releases TRH,

T3 & T4 help regulate Hypothalamus & pituitary: stimulates pituitary produces
metabolism, growth & maintain thyroid homeostasis TSH

development of the human (hypothalamic–pituitary–

TSH: stimulates the thyroid to
body thyroid (HPT) axis)
produce & release thyroid
hormones to reach normal levels
in the blood

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 PATO F I SI O L O G I K E LE N J A R TI RO I D

Tiroid: Memproduksi dan melepaskan T3 & T4

I II III

Hipotalamus: melepaskan TRH,

T3 & T4 membantu mengatur Hipotalamus & hipofisis: merangsang kel. Pituitari
metabolism, pertumbuhan & mempertahankan homeostasis menghasilkan TSH

perkembangan tubuh manusia tiroid (sumbu hypothalamic–

TSH: merangsang tiroid
pituitary–thyroid (HPT))
memproduksi & melepaskan
hormon tiroid untuk mencapai
kadar normal dalam darah

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GAMBAR 1.

Hypothalamic–
pituitary–thyroid axis
& homeostatis tiroid

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 PATHOPHYSIOLOGY OF THE THYROID
GLAND

PRIMARY NPC POST

RADIATION
HYPOTHYROIDISM
RT

Most common thyroid disorder Damage follicular epithelial Increased thyroid antibodies,
after head-neck RT cells, parenchyma & thyroid anti TPO and anti-AG
blood vessels

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 PATOFISIOLOGI KELENJAR TIROID

KNF PASCA
HIPOTIROIDISME
PRIMER RADIASI RT

Gangguan tiroid paling umum Merusak sel epitel folikuler, Peningkatan antibody tiroid,
pasca RT kepala-leher parenkim & pembuluh darah antiTPO & anti-AG
tiroid

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 LAB EXAM
TSH, free-T3 & free T4 examination
with/without clinical symptoms
DIAGNOSIS
CLINICAL HYPOTHYROIDISM
• High TSH, low T4 serum level
• Common symptoms: Fatigue,
weakness, cold intolerance, weight
gain, dry skin, edema, constipation,
neuromuscular symptoms

SUBCLINICAL
HYPOTHYROIDISM PREVALENCE
High serum TSH, low/normal T4 • Clinical hypothyroidism: found in
level without symptoms about 1-2% and is more common
• Subclinical hypothyroidism:
approximately 6% and is associated
with an increased risk of coronary
heart disease and death in patients
with high serum TSH concentrations
(≥10 mIU/L) in older women

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 PEMERIKSAAN LAB
Pemeriksaan TSH, free-T3 & free T4
dengan/tanpa gejala klinis
DIAGNOSIS
HIPOTIROIDISME SUBKLINIS
Kadar serum TSH tinggi, T4
rendah/normal tanpa gejala
HIPOTIROIDISME KLINIS
• Kadar serum TSH tinggi, T4 rendah
• Gejala umum: Lelah, lemah,
intoleransi dingin, penambahan berat
badan, kulit kering, edema,
konstipasi, gejala neuromuskular
PREVALENSI
• Hipotiroidisme klinis: ditemukan
sekitar 1-2% dan lebih sering terjadi
• Hipotiroidisme subklinis: sekitar 6%
dan berhubungan dengan peningkatan
risiko penyakit jantung koroner dan
kematian pada pasien dengan
konsentrasi TSH serum yang tinggi
(≥10 mIU/L) pada wanita yang lebih tua
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RADIATION-INDUCED
HYPOTHYROIDISM
BILATERAL NECK
LYMPHNODES STUDY​
Included in the clinical target Changes occur within 2 years
volume (CTV) after RT NPC

RT of the neck causes an Lin et al: 20%, 30% & 40%

unavoidable dose of radiation reduction in thyroid volume at
to the thyroid gland 6, 12 & 30 months,
respectively

There was a decrease in free-

T4 levels and an increase in
free-T3 levels after RT

Phenomenon: e.c thyroid

shrinkage

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RADIATION-INDUCED
HYPOTHYROIDISM
KGB LEHER BILATERAL STUDI​
Dimasukkan ke dalam volume Perubahan terjadi dalam 2
target klinis (CTV) tahun pasca RT KNF

Penyinaran RT pada leher Lin et al: reduksi volume tiroid

menyebabkan dosis radiasi 20%, 30% & 40% pada
yang tak terhindarkan pada masing-masing 6, 12 & 30
kelenjar tiroid bulan

Terjadi penurunan kadar free-

T4 dan peningkatan kadar
free-T3 pasca RT

Fenomena: e.c penyusutan

tiroid

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FACTORS RELATED TO RIHT RADIATION TECHNIQUE
IMRT & Inverse Planning:
maximize dose match to tumor,
minimize unnecessary dose to
surrounding critical structures

RADIATION DOSE
Radiation to the entire gland
volume at a total dose of 45 Gy
results in an estimated 8%
probability of clinical
hypothyroidism at 5 years

RESEARCH
According to the IMRT study on
NPC, the average thyroid dose
ranged from 43-54 Gy which
resulted in a high incidence of
RIHT of up to 54%.

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 TEKNIK RADIASI
IMRT & Inverse Planning:
FAKTOR TERKAIT RIHT
maksimalkan kesesuaian dosis
dengan tumor, meminimalisir
dosis yang tidak perlu ke
struktur kritis di sekitarnya

DOSIS RADIASI
Radiasi ke seluruh volume
kelenjar pada total dosis 45 Gy
menghasilkan perkiraan
kemungkinan hipotiroidisme
klinis 8% pada 5 tahun

PENELITIAN
Menurut penelitian IMRT pada
KNF, rata-rata dosis tiroid
berkisar antara 43-54 Gy yang
mengakibatkan tingginya insiden
RIHT hingga 54%

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 TABEL 1
Prediktor klinis dan dosimetrik untuk hipotiroidisme
akibat radiasi pada KNF
 TABLE 1
Clinical and dosimetric predictors of radiation-induced
hypothyroidism in NPC
Faktor tidak dapat dimodifikasi: usia, jenis kelamin, volume tiroid &
kadar TSH sebelum radiasi

TERKAIT RIHT
FAKTOR
Meminimalisir dosis radiasi yang tidak perlu ke tiroid: PENTING!!!

Cek teknik IMRT:

• Mencocokkan rencana IMRT dengan conventional anterior low-
neck field dengan midline shield, yang disebut IMRT split-file
• Menghilangkan pengobatan kelenjar getah bening level IV pada
penyakit T1
• Mengurangi tumpang tindih antara volume target perencanaan risiko
rendah (PTV-LR) dan kelenjar tiroid 23
Non-modifiable factors: age, sex, thyroid volume & TSH levels before
radiation

TO RIHT
FACTORS RELATED
Minimizing unnecessary radiation doses to the thyroid:
IMPORTANT!!!

Check IMRT technique:

• Matching the IMRT plan with a conventional anterior low-neck field
with a midline shield, the so-called split-file IMRT
• Eliminate treatment of level IV lymph nodes in T1 disease
• Reduces the overlap between the low-risk planning target volume
(PTV-LR) and the thyroid gland
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PREDICTIVE MODELS FOR RIHT

- there has recently been proposing the use of normal tissue

complication probability (NTCP) model to estimate risk of
complication

- The most common types of NTCP models are Lyman model,

logistic model, and logistic regression model.

- Baseline thyroid function test is required to exclude

preexisting thyroid dysfunction and not to overestimate the
incidence of RIHT after radiation.

8/ 03/ 20 XX PIT CH DECK 25

MODEL PREDIKTIF • Jenis NTCP: Lyman, model logistik & regeresi logistik
UNTUK RIHT • Sampai saat ini, hanya terdapat dua penelitian yang
NTCP: memperkirakan risiko berfokus pada pengembangan alat prediksi untuk RIHT
komplikasi
pada pasien NPC
Tujuan: menerjemahkan input
dosimetrik menjadi relevan secara
• Sebelum penerapan klinis: validasi eksternal
klinis • Tes fungsi tiroid: menyingkirkan riwayat disfungsi tiroid
sebelumnya
• Imunitas & radiogenomik: integrasi ke NTCP

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PREDICTIVE MODEL
FOR RIHT
NTCP: estimating the risk of
complications
Goal: translate dosimetric input
into clinically relevant
• NTCP type: Lyman, logistic model & logistic regression
• To date, only two studies have focused on developing
predictive tools for RIHT in NPC . Patients
• Before clinical application: external validation
• Thyroid function test: rule out previous history of
thyroid dysfunction
• Immunity & radiogenomics: integration into NTCP
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THANK YOU

ANY QUESTION?

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