The Role of Radiotherapy towards Pediatric Cancer

57 Agustinus Darmadi Hariyanto, Hari Murti Wijaya, Jellyca Anton, Seize Edwiena Yanuarta, Steven Octavianus, Handoko, Endang Nuryadi, Soehartati A. Gondhowiardjo

The Role of Radiotherapy towards Pediatric Cancer

Agustinus Darmadi Hariyanto, Hari Murti Wijaya, Jellyca Anton, Seize Edwiena Yanuarta, Steven Octavianus,
Handoko, Endang Nuryadi, Soehartati A. Gondhowiardjo
Radiation Oncology Integrated Service Installation, Faculty of Medicine, University of Indonesia, dr. Cipto Mangunkusumo Hospital,
Jakarta, Indonesia

Article informations: Abstract

Received: July 2020 Cancer is the leading cause of death in children worldwide. Pediatric cancer is chal-
Accepted: November 2020 lenging to detect early because it generally appears with signs and symptoms that are
not typical. The increase in cancer cases in pediatric must be followed by an increase
in cancer management in all fields of scientific disciplines. Radiation oncology, as
one of the areas of science, has an essential role in definitive, adjuvant, palliative,
and prophylactic cancer in pediatric. Apart from these uses, radiation management is
Correspondence:
a significant contributor to the complications of pediatric cancer survivors. Compli-
Prof. Dr. dr. Soehartati A. G, cations that arise can be in the form of growth retardation, tissue changes, secondary
Sp.Rad (K) Onk.Rad
cancer, neurocognitive changes, infertility, or other hormonal dysfunction and pre-
E-mail:
term labor. An increase in radiation techniques followed the development of treat-
[email protected]
ment machines able to reduce radiation-related morbidity and mortality rates. In pe-
diatric radiotherapy, the entire process from the pre-procedure anesthesia to radio-
therapy requires special attention. Psychological issues are also worth observing.
This study will briefly discuss these matters and the management of some of the
most common pediatric cancers in Dr. Cipto Mangunkusumo Hospital.

Keywords: pediatr ic cancer , r adiother apy, br ainstem glioma, nasophar yngeal car cinoma, r eti-
noblastoma, medulloblastoma, soft tissue sarcoma

Copyright ©2020 Indonesian Radiation Oncology Society

Background
Cancer is the leading cause of death in pediatric. It The most significant is Acute Lymphoid Leukemia
could happen in every cycle of human life, from the (ALL) with a 90% five-year survival rate.6 However,
beginning of life until the geriatric phase.1 In 2018, children with cancer in Low-middle Income Countries
Globocan estimated about 272.600 new cases, and (LMICs) have not got that same benefit and chances of
101.000 death in children age 0-19 years old are caused that developed science yet. The probability of death
by cancer. The most common malignancy in pediatric incidents of children who live in LMIC is fourfold
is leukemia, central nervous system tumor, and lym- higher than kids in High-Income Countries (HIC). The
phoma.2 Higher incident prediction is reported by main factor of death rate in pediatric cancer who lives
Baseline Model (BM) that is formed based on in LMIC is drug availability, drug insufficiency, lack of
America's Surveillance, Epidemiology and End Results Centers of Excellence for pediatric cancer, waiting list
(SEER) in 2015. The BM estimated about 360.114 problem because of an inadequate hospital bed, human
cancer cases in pediatric worldwide, 54% in Asia, and resources availability, especially pediatric oncologists,
28% in Africa region.3 In Indonesia, pediatric account- delayed diagnostic and relapse.6,7 Cancer's impact on
ed for 3%-5% from all cancer.4,5 child is very complex; cancer will significantly affect
World scientific development, especially in cancer, children's growth and development, less school attend-
could increase the survival rate in pediatric. In Europe, ance, and disability and eventually will affect the
Gatta et al. reported that 1,3,5 survival years rate in all country itself because the country will lose the momen-
types of pediatric cancer is 90,6%, 81%, and 77,9 %. tum for human development.
 Radioterapi & Onkologi Indonesia Vol.11 (2) Juli 2020:57-65 58

Radiotherapy is an integral part of pediatric cancer Table 1. Total pediatr ic patient in IPTOR at Dr . Cipto
treatment.8 Synergizing Radiation Oncology with other Mangunkusumo Hospital from 2008 until 2014
multidisciplinary significantly decreases the potential ICD
No Diagnosis n (%)
10
morbidity and mortality. The goal of radiation therapy
1 C71 Malignant neoplasm of brain 333 (44)
is to obtain optimum therapeutic ratio and lowering Malignant neoplasm of eye and
acute and late toxicity risk. This review will give aa 2 C69 131 (17)
adnexa
perspective, a strategy, and some significant contribu- Malignant neoplasm of nasophar-
3 C11 78 (10)
ynx
tion in radiation oncology towards the most common Malignant neoplasm of bone and
4 C40 38 (5)
cancer in our institution and the effect of radiotherapy articular cartilage of limbs
Malignant neoplasm of other con-
in pediatric cancer. This strategy and guideline might 5 C49
nective and soft tissue
33 (4)
benefit for radiotherapy centers in performing radio- 6 C42
Malignant neoplasm hematopoiet-
31 (4)
ic and reticuloendothelial system
therapy for each institution. Malignant neoplasm of other and
7 C76 14 (2)
ill-defined sites
Materials and Methods Malignant neoplasm of accessory
8 C31 11 (1)
sinuses
This retrospective analysis was taken from cancer Malignant neoplasm of bronchus
9 C34 11 (1)
registration in hospital and Instalasi Pelayanan Terpadu and lung
10 Other Neoplasm 71 (9)
Onkologi Radiasi (IPTOR) RSUPN Dr. Cipto
Mangunkusumo year 2008-2014. The data was
analyzed based on age and the most common cancer Treatment Recommendation
type treated by radiotherapy for curative or palliative Medulloblastoma
intense. Four types of most common cancer would be Medulloblastoma (MB) is the most common brain
reviewed towards radiotherapy treatment guideline cancer in pediatric cancer with a peak at 6-8 years old.9
based on literature review and International Atomic Clinical manifestations of MB are an increase in
Energy ( IAEA) Training course on Pediatric radiation intracranial pressure, cerebellum disorder, and cranial
Oncology RAS 6086, that was held in Jakarta on nerve disorder.10 The treatment for MB is a
September, 2nd-6th, 2019 combination of surgery, radiation, and chemotherapy.
The risk level of MB is divided into an average risk
Results (age ≥3 years old, M0, local, gross total /near-total
Demography characteristic resection, remaining tumor <1,5 cm2) and high risk
From January 2008 until December 2014, there are (age <3 years old, >M0, disseminated, subtotal
2.986 children diagnosed with cancer, and 751 children resection/biopsy, remaining tumor>1,5 cm2, anaplastic
are treated with radiotherapy (RT). The most pediatric type/ large cell).10-12 The five –year survival rate for the
cancer that treated with RT is central nervous system average-risk group is 80% and 60-65% for the high-
malignancy (n=333;44%), eye and adnexa malignancy risk group.11 The goal of the operative procedure is
(n=131,17%), nasopharyngeal carcinoma (n=78;10%) optimum resection followed by radiation at the
and bone and soft tissue malignancy (n=71,9%). craniospinal axis and booster for the remaining tumor.

Figure 1. Total new cases of pediatr ic cancer tr eated by RT at Dr . Cipto Mangunkusumo Hospital fr om 2008 until 2014
 The Role of Radiotherapy towards Pediatric Cancer
59 Agustinus Darmadi Hariyanto, Hari Murti Wijaya, Jellyca Anton, Seize Edwiena Yanuarta, Steven Octavianus, Handoko, Endang Nuryadi, Soehartati A. Gondhowiardjo

Radiation is given via craniospinal irradiation (CSI) Pontine Glioma (DIPG) is still poor, with a survival
with dosage 23,4 Gy if followed by chemotherapy and rate of <10 % even with aggressive medication.
35-36 Gy if not followed by chemotherapy. Booster However, focal and exophytic brain stem tumor's
dosage is given to fossa posterior and the remaining prognosis is quite good, with a reported survival rate
tumor with maximal dose at 54-55 Gy.10 between 50-100%.15-18
The outcome of CSI lower dose in the average-risk Brain stem glioma, including low-grade Focal Brain
patient group is even if given without chemotherapy, Stem Glioma/FBSG (WHO type I-II) and high-grade
the Event Free Survival (EFS) will be the same as if the DIPG. Brain stem tumors developed in a crucial and
chemotherapy is given along with radiation and post- eloquent area. Usually, FBSG developed symptoms
radiation.8 There are no different EFS between post- within three months, and DIPG diagnosed within 3-6
radiation chemotherapy and chemotherapy pre months after the first symptoms appear.16,17
radiation.8 The outcome of postponed post-operative Children with brain stem glioma usually have a prior
radiation will not be as good as immediate post- neurologic disorder such as eyeball movement,
operative radiation followed by chemotherapy.13 diplopia, unsymmetrical smile, equilibrium disorder,
The radiation target of CSI is the whole CSF area. The and hemiparesis. The triad of clinical symptoms is
booster is given to the whole fossa posterior and the cranial neuropathy, ataxia, and long tract sign. At least
tumor bed. Clinical Target Volume (CTV) (Table 2) two-thirds of those symptoms are assessed to diagnose
include the cribriform plate, optical canal of sphenoid, brain stem glioma clinically.15,19 Biopsy no needs to be
superior orbital fissure, foramen rotundum, foramen performed if the patient shows classic symptoms and
ovale, internal auditory meatus, jugular foramen, and typical imaging. This thing is related to post-biopsy
hypoglossal canal. The PTV limit is according to each complication risk; also, the aggressive operative
department policy, usually for CTVcranial is 3-5 mm procedure would not be done.15,18 MRI is the golden
and CTVspinal is 5-8 mm. Delineated Organ at Risk standard in BSG characterization and excellent
(OAR) is an eyeball, lens, parotid gland and modality for assessing therapy responsiveness and
submandibular, larynx, esophagus, thyroid and prognosis.
women's breast, lung, liver, heart, gaster, colon, Surgery is a preferable choice, if possible. Radiation is
pancreas, kidney and gonad. The radiation technique is an alternative for non-operable patients or patients with
3DCRT, IMRT, VMAT, Tomotherapy and proton progressive disease after the procedure performed. In
therapy.14 the delineation process, MRI Imaging should combine

Table 2. Guideline of delineated CSI accor ding to SIOPE and COG tr ials

Source: reference no. 14

Brainstem Glioma with the CT scan imaging. Gross Tumor Volume

Around 12,4 % of all central nervous system tumors in (GTV) best defined in T2-weighted or Flair MRI. The
children from 0-14years old are developed in the border of CTV is 1-1,5cm, which anatomically
brainstem. The average age of children with brain stem bordered by bone and sometimes tentorium. Planning
glioma is 6-7 years old, with an equal ratio between Target volume is 0,3-0,5 cm. Using a sophisticated
girls and boys. The prognosis of Diffuse Intrinsic technique like IMRT is needed to reduce preparation
 Radioterapi & Onkologi Indonesia Vol.11 (2) Juli 2020:57-65 60

time that might delay the treatment process. Usually, nerve. The loco-regional spread occurs with direct
the dosage of RT is 30-31 fractions for six weeks.16,20,21 extension to the orbital and preauricular lymph nodes.
An alternative fractionation schedule has been studied The extra orbital disease manifested as intracranial
towards patients with DIPG. Hyperfraction RT 1-1,26 spreading and hematogenic metastasis to the bone,
Gy is given twice a day with a total dosage until 78 Gy bone marrow and liver.22,24
in order to increase the control tumor. In much The main goal of RB management is to increase the
continuous research in North America in the 1980- survival rate, eyesight preservation, and minimalize
1990s, dosage 76-78 Gy does not show any benefit; toxicity and side effect.22,24,25 The treatment is different
instead, more prominent morbidity are appearing, such for each patient depends on unilaterality, eyesight
as prolonged steroid use and the vascular event is potential (Reese-Ellsworth classification), stage's
found within the study. RT with an accelerated fraction disease (International Retinoblastoma Staging System
(common fraction 1,8 Gy which given twice a day) dan International Intraocular Retinoblastoma
with total dosage 48,6-50,4 Gy. A study in England Classification).26–28
shows that medication method with fractionation is not Radiotherapy is an effective modality for RB
superior, although it can be tolerated and considered treatment. Indication RT to RB is grade A/grade B RB
favorable because the patient and their family can with progressive local tumor after focal therapy (15%);
spend less time on medication procedure. Hypofraction RB multifocal and patients with near macula tumor or
RT also has been studied. Compared to conventional optic nerve with goal eyesight preservation (20%);
RT in one prospective study, hypofraction RT with large tumor and extension to vitreous which not
total dose 39-45 Gy (3 Gy once a day) is also safe and responds to systemic chemotherapy (40%); extraocular
effective.18 RB (post-operative RT); and palliative RT.25 RT dose
A systematic review was written by Matthew Gallitto is depending on International Intraocular
et al. in 2019 about the role of radiotherapy in DIPG Retinoblastoma Classification; total dosage 45 Gy with
management is, there is no significant difference 1,8 Gy/fraction for RB classification 1, classification 2,
between conventional radiation with hyperfraction and and post-operative with the microscopic residual
one-year survival rate (30,9% vs. 27%) or median time lesion. The other option for RB classification 3,4,5 and
progressivity (6 vs. 5 months). Higher hyperfraction gross residual RT post-operative is total dosage 50,4
(total dose 75,6 Gy given twice a day in 60 fractions) Gy with 1,8 Gy /fraction. The target volume for RT is
did not increase the outcome of DIPG. Otherwise, the whole retina through ora serata and extends to a
hypofraction radiation is not statistically inferior if minimal 1 cm from the optic nerve with 3D technique
compared with conventional radiation.17 Large scale or IMRT. While doing RT planning, very important to
exploration, multi-institutional, is needed to identify an minimalize spreading dosage towards the contralateral
optimal technique, total dose, and fractionation for eye, optic chiasma, pituitary gland, and spinal cord.25
definitive radiation in DIPG.
Nasopharyngeal carcinoma
Retinoblastoma About 5 % of primary malignant neoplasm developed
Retinoblastoma (RB) is the most common eye in the head and neck area, whereas nasopharyngeal
malignancy in pediatric, presenting 2,5-4% form total carcinoma (NPC) represents around 2% in the
pediatric cancer and 11% cancer in the first year of children's age group. The incident increases gradually
life.22 RB incidence in worldwide constantly sit in 1 along as they get old. In adults, Nasopharyngeal
per 15.000-20.000 live births rate, around 9000 new carcinoma is a common type of cancer in head and
cases every year.23 In a developed country, RB is neck with the variant incident rate worldwide.29 NPC in
diagnosed in an early stage (intraocular). Nevertheless, children is different from adults towards correlating
in low-middle income countries (LMIC), 60-90 % of with EBV, non-differentiated histology type and
children come to the doctor with an extraocular tumor. advance loco-regional incident rate.30,31
The critical treatment for RB depends on the capability SEER study aims to compare NPC in pediatric and
of detecting and perform therapy in early- adult found that children and adolescents showing a
stage/intraocular tumors. The staging is correlated with better result than adults, although there is advanced
delayed diagnosis, growth, and development from the disease. This patient group has higher long term
retina that only happens after the tumor reaches a complication risk, including increasing secondary
bigger intraocular dimension.22 The extension of RB is cancer risk.32-34
started with spreading to choroid and sclera and optic
 The Role of Radiotherapy towards Pediatric Cancer
61 Agustinus Darmadi Hariyanto, Hari Murti Wijaya, Jellyca Anton, Seize Edwiena Yanuarta, Steven Octavianus, Handoko, Endang Nuryadi, Soehartati A. Gondhowiardjo

The early new diagnosis gold standard of NPC is with Nasal cavity – posterior part
nasopharyngeal endoscopy biopsy. Radiologic imaging At least 5 mm from choana
might help in staging and disease spreading. Compared Maxillary sinus – posterior part
with the CT scan, MRI is an excellent modality. T1 At least 5 mm from the posterior wall
MRI will show asymmetric mass, which is hypo- Posterior ethmoid sinus
intensity, and figure T2 shows mild hyperintensity. Vomer included
Mass invasion to the skull base is easier to detect by Skull Base
MRI because of the clivus bone marrow signal change Foramen ovale included rotundum, lacerum, a
(decreasing in T1 and increasing in T2). Besides those nd petrous tip
imaging modalities, PET CT is also used for local and Cavernous sinus
early assess distant metastasis.35 If T3-4 (only involved side)
Treatment for pediatric nasopharyngeal carcinoma is Pterygoid fossa and parapharyngeal space
complying with adult's nasopharyngeal carcinoma Whole
guideline with early chemotherapy tendency to Sphenoid sinus
neoadjuvant form. In the last couple of years, the Inferior ½ if T1-2; whole if T3-4
congruent superiority of chemoradiation / concurrent Clivus
chemoradiotherapy (CCR) towards adult NPC was 1/3 if there is no invasion; whole if there is an
proven. This development of CCR usage to adults with invasion
NPC is studied. One of them is the ARAR 0331 CTV nodal – moderate dose (CTVn2)
protocol developed by Children's Oncology Group to CTVn1 + 5 mm
assess chemotherapy induction feasibility and benefit, Lymphatic node–bilateral retropharyngeal,
followed by CCR. From this study, the induction of level II, III, and Va
chemotherapy and CCR is giving an excellent outcome Level VIIb + at least one level ipsilateral under
near 90% in 5 years, and reducing radiation dose is the involved level
considered to patient who is responsive toward Level Ib
induction chemotherapy. Operative procedures in NPC Include if involved: the submandibular gland,
usually could not be performed because of the complex the flowing structure to level Ib as first echelon
anatomical area. Therefore radiation is an option. (oral cavity, ½ anterior nasal cavity), level II
Radical neck dissection is considered when the primary with extracapsular extension.
tumor has been controlled, or there is persistent neck CTV nodal – low dose (CTVn3)
node after chemoradiation or neck local relapse after Level IV and Vb through clavicular regio
radiation.29,35,36 Ignore if N0 or N1 based on retropharyngeal
Radiotherapy in pediatric NPC is given with a total lymphatics node involvement.
dose of 50-70Gy in 33-35 Gy fraction to the primary
tumor and neck lymph node.33,37 These are the term of Soft tissue sarcoma
the delineated guideline in pediatric NPC, which Soft tissue sarcoma (STS) is a group of malignant
comply with the adult delineated guideline.37 neoplasm that comprises embryonic mesenchymal
tissue during the differentiated process to become
Primary CTV dan high dose node (CTVp1 and muscle, fascia, and fat.38 This malignancy is around 6-8
CTVn1) % of total pediatric cancer, and 50-60 % is
CTVp1 : distance from GTVp Rhabdomyosarcoma (RMS). Furthermore, the rest of it
GTVp + 5 mm (± whole nasopharyngeal), is known as non-RMS STS (NRSTS), a classification
could reduce to minimum 1 mm (if close to the that comprises all kind of soft tissue tumor that is rare
critical organ) including Ewing sarcoma, fibrosarcoma, synovial
CTVn1 : distance from GTVn sarcoma ad malignant peripheral nerve sheath tumor
GTVn + 5 mm (consider 10 mm if there is (MPNSTSs).39 Two-thirds of RMS are diagnosed
extracapsular extension) before age six years old, and the incident rate is
Primary CTV - moderate dose (CTVp2) decreased as they got old. Otherwise, adolescents have
Margin from GTV a higher risk of developing NRSTS than a younger
GTVp + 10 mm + whole nasopharyngeal, c child. RMS can develop in any body area, including
ould reduce to minimum 2 mm (if close to the head and neck (35%), genitourinary (24%) and
critical organ ) extremity ( 19%)
 Radioterapi & Onkologi Indonesia Vol.11 (2) Juli 2020:57-65 62

RMS needs a multidiscipline approach between azoospermia.46,48 Ovarium function disorder occurs if
surgery, chemotherapy, and RT. RT itself is the pillar the radiation dose is 12-15 Gy48 with 2-12 years
for increasing local control. Treatment of RMS healing period.46 If the heart obtains a dose of 2,5-3
depends on the risk stratification based on Intergroup Gy, it will cause an increase in coronary heart risk,
Rhabdomyosarcoma Study (IRS) Clinical Grouping, stroke and heart disease with dose 1-4 Gy in vascular,
TNM staging, and histopathology.41 IRSG Study cataract with 2,3-3 Gy, diplopia and dry eye with dose
establishes the standard guideline for RMS dose in 5-12 Gy,48 Lung cancer risk are increasing with dose
pediatric; 50,4 Gy and 41,4 Gy with 1,8 Gy per fraction >9 Gy in post-radiation Hodgkin's patient. The
for gross tumor and microscopic disease, advanced effect will aggravate other cancer therapy
respectively.42 RMS with low group risk stratification modalities.
based on D9602 and ARST0331 study criteria could be A carcinogenic effect from radiation, chemotherapy,
given a reduced total dose to 36-45 Gy.43 The five-year and a combination of both can cause secondary
survival rate and local control in RMS are good. The malignancy. The risk is getting higher 3-6 fold in
survival rate is 90-95% for low-risk stratification, 68- pediatric cancer survival.47 Secondary malignant latent
78% in a mild risk group, and 25% in a high risk growth happens 7-20 years after the primary tumor was
group.42 diagnosed.47,48 The most common type is secondary
Determine the target delineation of RMS is essential. AML, which related to chemotherapy, and could
Basic Gross Tumor Volume (GTV) delineation is happen at least three months after radiation with a 10-
diagnostic imaging before the treatment. CTV is year peak risk. The second most common is a
determined by giving margin +2cm from GTV, adding secondary solid tumor, which depends on radiation
post-operative area, and the involved lymph nodes. dose, with median 9,5 years.48
PTV is determined with giving margin 5 mm towards Nevertheless, this radiation is very much needed
CTV.44 IMRT is preferable for Head and neck RMS, because it could treat tumors effectively. Radiations
with a reduction to 1 cm CTV margin giving 95% 3- also related to long term survival rates. Pediatric cancer
year control loco-regional result with minimum survival is a unique population with a unique problem
toxicity.45 and need. With the increase of the outcome, there is
COG study ARST0332 determines treatment still some problem that is not solved yet, so research
recommendation for RT and chemoradiation in NRST. and adequate intervention is still needed to lowering or
Indication determined by local vs. metastasis, prevent it.
operability status, post-operative margin status, grades,
and tumor size (Figure 2). In a delayed plan operative, Special consideration
neoadjuvant chemoradiation with 45 Gy is preferable. Children are not adult miniature. There are many
Tumor with positive post-operative margin and gross physiologic, anatomic, and psychological diverse,
tumor, so, the preferable RT is a total dose for each is which make treatment approach toward children is
55,8 Gy and 64,8 Gy, respectively.8 different. Mostly pediatric cancer is sensitive to
radiation, but on the other side, the toxicity effect and
Toxicity and secondary malignancy advance is being distinctive considered in RT benefit to
Pediatric cancer survivors are facing the next effect of pediatric cancer.50
prior cancer therapy.46,47 Various type of tumor, Limited sources are the main challenge in radiotherapy
location and body shape are correlated with various for children in LMIC countries, particularly Indonesia.
tumor radiosensitivity and combination with other Pediatric cancers need a specific approach, which
treatment. Radiation therapy that is given in growthful could reduce adverse effects for the body and children
and immature tissue will cause a significant anatomic psychosocial. This approach has to prioritize the
and functional problem.48 maximal clinical outcome and excellence of patient
The radiation late effect is different for each dose, safety and quality assurance.51 Prophylaxis and trauma
organ disposition, and age spectrum.48,49 The arising psychological management through family and staff
effect can be seen as growth resistance, tissue change, support is essential during the journey.
secondary cancer, neurocognitive change, infertility, or The benefit of radiotherapy with the best technique is
other hormonal dysfunction, and premature labour. 20 the top priority in pediatric cancer management. The
Gy radiation dose towards breast could stop its growth, goal is to maximize therapy dose towards tumor and
while 10 Gy towards breast will cause hypoplasia.46 minimalize the effect on healthy tissue.52 So that,
Low dose ( 2-3 Gy) to testicle will cause permanent conformal RT with IMRT, IGRT, and SRS/SRT is a
 The Role of Radiotherapy towards Pediatric Cancer
63 Agustinus Darmadi Hariyanto, Hari Murti Wijaya, Jellyca Anton, Seize Edwiena Yanuarta, Steven Octavianus, Handoko, Endang Nuryadi, Soehartati A. Gondhowiardjo

top recommendation in RT treatment. This minimalize risk and save planned anesthesia
recommendation also needs adequate human source procedures. Kids friendly RT procedure room and save
through continuous training (multidiscipline team, anesthesia with scared distraction equipment during the
medical staff, anesthesia, nurse, medical physician therapy is needed. Providing particular anesthesia
radiation technologist) and adequate immobilized recovery room and resuscitation with adequate
equipment.51 According to the recommendation, an emergency equipment for pediatric cancer.51
integrated referral to a qualified facility is a must for Special attention to the psychological issue is needed in
therapeutic goals in pediatric cancer management. pediatric cancer comprehensive management. Pediatric
Immobilization itself is a challenging moment for cancer generates a serious problem in the children
giving RT treatment to children. Children under five themselves and their families. Children could not
years old have a difficult time in immobilization during choose their medications, and parent is the key to
simulation and therapy; in these circumstances, mostly decide the therapy. Healing chance, the growth,
children having anxiety and afraid because of being development, and their next quality of life significantly

Figure 2. Gr oup Risk and Tr eatment Guideline of NRSTS based on Childr en Oncology Gr oup ARST 0332
Source: reference no. 8

apart from their parents and uncomfortable medical depend on the parent's choice. The interpersonal
procedure. Anesthesia procedure is needed to maintain approach and empathy from dedicated medical staff
their position and immobilization during the process. during the medication process have to make sure that
Integrated and save anesthesia procedure is the key to the parents got accurate information and fully
minimalize children's trauma and risk. Anesthesia pre- understand the effect to the child so that information
procedure assessment must as accurate as possible to will help the parents to decide the right decision.
 Radioterapi & Onkologi Indonesia Vol.11 (2) Juli 2020:57-65 64

Conclusions 106.
Multidisciplinary care is a must in managing pediatric 13. Kortmann RD, Kühl J, Timmermann B, Mittler U, Urban
cancer. Cancer therapy needs a particular diagnostic C, Budach V, et al. Postoperative neoadjuvant chemotherapy
before radiotherapy as compared to immediate radiotherapy
and therapeutic and also the ability to manage potential
followed by maintenance chemotherapy in the treatment of
complications. RT has a significant positive effect on
medulloblastoma in childhood: Results of the German
the development of pediatric cancer treatment; the prospective randomized trial HIT ’91. Int J Radiat Oncol
newest effective technique increases survival rate and Biol Phys. 2000;46(2):269–79.
cancer control, decrease late side effect and has an 14. Ajithkumar T, Horan G, Padovani L, Thorp N,
excellent palliative modality. Timmermann B, Alapetite C, et al. SIOPE – Brain tumor
group consensus guideline on craniospinal target volume
References delineation for high-precision radiotherapy. Radiother
1. World Health Organization. WHO | Global Initiative for Oncol. 2018;128(2):192–7.
Childhood Cancer [Internet]. WHO. World Health 15. Reaman GH, Smith FO, Merchant TE, Kortmann R-D.
Organization; 2018 [cited 2019 Oct 1]. Pediatric Oncology Series Editors: Pediatric Radiation
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Oncology [Internet]. Pediatric Oncology Series Editors:
Jemal A. Global cancer statistics 2018: GLOBOCAN Pediatric Radiation Oncology. 2018. 3–10 p.
estimates of incidence and mortality worldwide for 36 16. Green AL, Kieran MW. Pediatric Brainstem Gliomas:
cancers in 185 countries. CA Cancer J Clin [Internet]. New Understanding Leads to Potential New Treatments for
2018;68(6):394–424. Two Very Different Tumors. Curr Oncol Rep. 2015;17(3).
3. Johnston WT, Erdmann F, Newton R, Steliarova-Foucher 17. Gallitto M, Lazarev S, Wasserman I, Stafford JM,
E, Schüz J, Roman E. Childhood cancer: Estimating regional Wolden SL, Terezakis SA, et al. Role of Radiation Therapy
and global incidence. Cancer Epidemiol [Internet]. in the Management of Diffuse Intrinsic Pontine Glioma: A
2020;(December):101662. Systematic Review. Adv Radiat Oncol. 2019;4(3):520–31.
4. Agustina J, Sinulingga DT, Suzanna E, Tehuteru E, 18. Mahajan A, Paulino A. Radiation oncology for pediatric
Ramadhan R, Kadir A. Epidemiology of Childhood Cancer CNS tumors. Radiation Oncology for Pediatric CNS
in Indonesia: Study of 14 Population Based Cancer Tumors. 2017. 1–639 p.
Registries. J Glob Oncol [Internet]. 2018 Oct 28 [cited 2019 19. Anacak Y. Radiotherapy for Brain Stem Gliomas. In
Jul 23];(4_suppl_2):67s-67s. Jakarta: IAEA Training Course for Pediatric Radiation
5. Gatot D, Windiastuti E. Treatment of childhood acute Oncology; 2019.
lymphoblastic leukemia in Jakarta: Result of modified 20. Tinkle CL, Simone B, Chiang J, Li X, Campbell K, Han
Indonesian National Protocol 94. Paediatr Indones [Internet]. Y, et al. Defining Optimal Target Volumes of Conformal
2016 Oct 18;46(4):179. Radiation Therapy for Diffuse Intrinsic Pontine Glioma. Int J
6. Gatta G, Botta L, Rossi S, Aareleid T, Bielska-Lasota M, Radiat Oncol Biol Phys. 2020;106(4):838–47.
Clavel J, et al. Childhood cancer survival in Europe 1999– 21. Brady LW, Heilman HP, Molls M, Neider C. Pediatric
2007: results of EUROCARE-5—a population-based study. Brain Tumors. In: Lu JJ, Brady LW, editors. Decision
Lancet Oncol [Internet]. 2014 Jan;15(1):35–47. Making in Radiation Oncology. 2011th ed. Springer-Verlag
7. Howard SC, Zaidi A, Cao X, Weil O, Bey P, Patte C, et Berlin Heidelberg; 2011. p. 1011–36.
al. The My Child Matters programme: effect of public– 22. Gupta S, Howard SC, Hunger SP, Antillon FG, Metzger
private partnerships on paediatric cancer care in low-income ML, Israels T, et al. Treating Childhood Cancer in Low- and
and middle-income countries. Lancet Oncol [Internet]. Middle-Income Countries. Dis Control Priorities, Third Ed
2018;19(5):e252–66. (Volume 3) Cancer. 2015;121–46.
8. Breneman JC, Donaldson SS, Constine L, Merchant T, 23. Kivela T. The epidemiological challenge of the most
Marcus K, Paulino AC, et al. The Children’s Oncology frequent eye cancer: retinoblastoma, an issue of birth and
Group Radiation Oncology Discipline: 15 Years of death. Br J Ophthalmol [Internet]. 2009 Sep 1;93(9):1129–
Contributions to the Treatment of Childhood Cancer. Int J 31.
Radiat Oncol Biol Phys [Internet]. 2018;101(4):860–74. 24. Kodrat H, Gondhowiardjo S. Radioterapi & Onkologi
9. Northcott PA, Robinson GW, Kratz CP, Mabbott DJ, RADIOTERAPI PADA RETINOBLASTOMA. Radioter
Pomeroy SL, Clifford SC, et al. Medulloblastoma. Nat Rev dan Onkol Indones. 2013;4(1):17–23.
Dis Prim. 2019;5(1). 25. Siddhartha Laskar. Radiotherapy for Retinoblastoma. In:
10. Anacak Y. Pediatric Medulloblastoma & Ependymoma Siddhartha Laskar, editor. IAEA Training Course for
and CSI. In Jakarta: IAEA Training Course for Pediatric Pediatric Radiation Oncology. Jakarta: Siddhartha Laskar;
Radiation Oncology; 2019. 2019.
11. Udaka YT, Packer RJ. Pediatric Brain Tumors. Neurol 26. Reese AB, Ellswoth RM. The evaluation and current
Clin. 2018;36(3):533–56. concept of retinoblastoma therapy. Trans Am Acad
12. Edmond JC. Pediatric brain tumors: The neuro- Ophthalmol Otolaryngol [Internet]. 67:164–72.
ophthalmic impact. Int Ophthalmol Clin. 2012;52(3):95– 27. Chantada G, Doz F, Antoneli CBG, Grundy R, Clare
 The Role of Radiotherapy towards Pediatric Cancer
65 Agustinus Darmadi Hariyanto, Hari Murti Wijaya, Jellyca Anton, Seize Edwiena Yanuarta, Steven Octavianus, Handoko, Endang Nuryadi, Soehartati A. Gondhowiardjo

Stannard FF, Dunkel IJ, et al. A proposal for an international 42. Breneman JC, Lyden E, Pappo AS, Link MP, Anderson
retinoblastoma staging system. Pediatr Blood Cancer JR, Parham DM, et al. Prognostic Factors and Clinical
[Internet]. 2006 Nov;47(6):801–5. Outcomes in Children and Adolescents With Metastatic
28. A LM. Intraocular Retinoblastoma: the Case for a New Rhabdomyosarcoma—A Report From the Intergroup
Group Classification. Ophthalmol Clin North Am [Internet]. Rhabdomyosarcoma Study IV. J Clin Oncol [Internet]. 2003
2005 Mar;18(1):41–53. Jan 1;21(1):78–84.
29. Swain SK, Samal S, Anand N, Mohanty J. Pediatric 43. Breneman J, Meza J, Donaldson SS, Raney RB, Wolden
nasopharyngeal carcinoma. Int J Heal Allied Sci. S, Michalski J, et al. Local Control With Reduced-Dose
2020;9(1):1–6. Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report
30. González-Motta A, González G, Bermudéz Y, From the Children’s Oncology Group D9602 Study. Int J
Maldonado MC, Castañeda JM, Lopéz D, et al. Pediatric Radiat Oncol [Internet]. 2012 Jun;83(2):720–6.
Nasopharyngeal Cancer: Case Report and Review of the 44. Michalski JM, Meza J, Breneman JC, Wolden SL, Laurie
Literature. Cureus. 2016;8(2). F, Jodoin MA, et al. Influence of radiation therapy
31. Laskar S, Sanghavi V, Muckaden MA, Ghosh S, Bhalla parameters on outcome in children treated with radiation
V, Banavali S, et al. Nasopharyngeal carcinoma in children: therapy for localized parameningeal rhabdomyosarcoma in
Ten years’ experience at the Tata Memorial Hospital, Intergroup Rhabdomyosarcoma Study Group trials II
Mumbai. Int J Radiat Oncol Biol Phys. 2004;58(1):189–95. through IV. Int J Radiat Oncol [Internet]. 2004
32. Sultan I, Casanova M, Ferrari A, Rihani R, Rodriguez- Jul;59(4):1027–38.
Galindo C. Differential features of nasopharyngeal 45. Wolden SL, Wexler LH, Kraus DH, Laquaglia MP, Lis
carcinoma in children and adults: A SEER study. Pediatr E, Meyers PA. Intensity-modulated radiotherapy for head-
Blood Cancer. 2010 Apr;55(2):279–84. and-neck rhabdomyosarcoma. Int J Radiat Oncol [Internet].
33. Laskar S. No Title. In: Radiation Therapy in Paediatric 2005 Apr;61(5):1432–8.
Nasopharyngeal Carcinoma. Jakarta: IAEA Training Course 46. Mittal N, Kent P. Long-Term Survivors of Childhood
for Pediatric Radiation Oncology; 2019. Cancer: The Late Effects of Therapy. Pediatr Cancer Surviv.
34. Richards MK, Dahl JP, Gow K, Goldin AB, Doski J, 2017
Goldfarb M, et al. Factors associated with mortality in 47. Arain A, Herman T, Matthiesen C. Late Effects of
pediatric vs adult nasopharyngeal carcinoma. JAMA Radiation Therapy in Pediatric Cancer Survivors. J Okla
Otolaryngol - Head Neck Surg. 2016;142(3):217–22. State Med Assoc. 2015;108(4):129–35.
35. Muzaffar R, Vacca F, Guo H, Mhapsekar R, Osman 48. Anacak Y. Late Effects and Secondary Cancers. In:
MM. Pediatric nasopharyngeal carcinoma as seen on 18F- IAEA Training Course for Pediatric Radiation Oncology.
FDG PET/CT. Front Oncol. 2019;9(MAR):18–21. Jakarta: IAEA Training Course for Pediatric Radiation
36. Rodriguez-Galindo C, Krailo MD, Krasin MJ, Huang L, Oncology, 2-6 Sept 2019; 2019.
Beth McCarville M, Hicks J, et al. Treatment of childhood 49. Krasin MJ, Constine LS, Friedman DL, Marks LB.
nasopharyngeal carcinoma with induction chemotherapy and Radiation-Related Treatment Effects Across the Age
concurrent chemoradiotherapy: Results of the Children’s Spectrum: Differences and Similarities or What the Old and
Oncology Group ARAR0331 study. J Clin Oncol. Young Can Learn from Each Other. Semin Radiat Oncol.
2019;37(35):3369–76. 2010;20(1):21–9.
37. Hansen EK, Roach III M. Handbook of Evidence-Based 50. Salminen E, Anacak Y, Laskar S, Kortmann RD,
Radiation Oncology. Hansen EK, Roach III M, editors. Raslawski E, Stevens G, et al. Twinning partnerships
Handbook of Evidence-Based Radiation Oncology. Cham: through International Atomic Energy Agency (IAEA) to
Springer International Publishing; 2018. 145–158 p. improve radiotherapy in common paediatric cancers in low-
38. Sangkhathat S. Current management of pediatric soft and mid-income countries. Radiother Oncol [Internet].
tissue sarcomas. World J Clin Pediatr [Internet]. 2009;93(2):368–71.
2015;4(4):94. 51. Royal College of Radiologists, Society and College of
39. Kaatsch P. Epidemiology of childhood cancer. Cancer Radiographers, Institute of Physics and Engineering in
Treat Rev [Internet]. 2010 Jun;36(4):277–85. Medicine, Children’s Cancer and Leukaemia Group. Good
40. Terezakis S, Ladra M. Pediatric Rhabdomyosarcoma. In: practice guide for paediatric radiotherapy Second edition. R
Pediatric Radiation Oncology [Internet]. Springer Coll Radiol [Internet]. 2018;(August).\
International Publishing; 2018. p. 21–43. 52. Constine LS, Ronckers CM, Hua CH, Olch A, Kremer
41. Maurer HM, Intergroup Rhabdomyosarcoma Study. The LCM, Jackson A, et al. Pediatric Normal Tissue Effects in
intergroup rhabdomyosarcoma study II: Objectives and the Clinic (PENTEC): An International Collaboration to
study design†. J Pediatr Surg [Internet]. 1980 Jun;15(3):371– Analyse Normal Tissue Radiation Dose–Volume Response
2. Relationships for Paediatric Cancer Patients. Clin Oncol
[Internet]. 2019;31(3):199–207.