Radioterapi Pada Kanker Anak

RS Kanker Dharmais
Pusat Kanker Nasional
 Modalitas terapi kanker

Chemotherapy Radiotherapy

Surgery
Targeted Therapy Immuno Therapy

Stem Cell Transplant

Hormonal Therapy
 Radiotherapy
• Terapi menggunakan sinar pengion untuk mengendalikan atau
membunuh sel tumor ganas

Perez & Brady’s. Principles and Practice of Radiation Oncology. 6 th ed

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Gunderson & Tepper. Clinical Radiation Oncology. 4th ed
Kyu HH, Stein CE, Pinto CB et al. Causes of death among children aged 5–14 years in the WHO European Region:
a systematic analysis for the Global Burden of Disease Study 2016. The Lancet 2018.
TRENDS IN CHILDHOOD CANCER MORTALITY
RATES
• The mortality rate from childhood cancer has fallen dramatically in
the US.
• Impressive gains posted for
• Acute Lymphocytic Leukemia (ALL),
• Bone tumors (predominantly Osteosarcoma and Ewing sarcoma),
• Hodgkin disease, non-Hodgkin lymphoma,
• Soft tissue sarcomas (including Rhabdomyosarcoma and
nonrhabdomyosarcoma soft tissue sarcomas), and
• Wilms tumor.
• In general, however, the diagnosis and treatment of childhood
cancer has been one of the success stories of modern medicine.
 Leukemia : Sarcoma (Soft Tissue) :
ALL, AML RMS, MPNST
CNS (Brain Tumors) : Kidney :
Meduloblastoma, Ependymoma,
Germinoma Wilms (Nephroblastoma)

Retinoblastoma Liver :
(Eyes) Hepatoblasstoma, Hepatocellular Ca

Neuroblastoma Germ Cell Tumors :

Seminoma, yolk sac, teratoma

Lymphoma :
Hodgkin, Non Hodgkin
Sarcoma (Bones) :
Ewing, Osteosarcoma
Misc :
Thyroid, Nasopharynx,
Pulmonary Blastoma,
Breast Cancer, LCH,
etc.
CURE DEFINITION IN PEDIATRIC
ONCOLOGY?
• Easson and Russel definition for cure: “We can speak of cure when in time—
probably a decade or so after treatment—there remains a group of disease-
free survivors whose progressive death rates from all causes is similar to
that of a normal population of the same sex and age constitution.”
• Patients and clinicians, during the 1960s and 1970s, became comfortable
with transitioning from the concept of “indefinite remission” to “cure”
• For each child with cancer and his or her family, the meaning of cure is
different. For some patients, it is the knowledge that the disease is gone
and never coming back.
• To others, it is the statement that they are well today and want to be so
tomorrow.
• For all children with cancer, hope is the common denominator and getting
on with life is the goal.
Leukemia
• ALL :
• Preventive/relapse Cranial or Craniospinal Irradiation (18-24Gy/1.5Gy per day) in High Risk
CNS relapse (CNS 3)
• (+) Superior disease control ; (-) late toxicities (neurologic deficits)
• Addition to chemo for repeated testicular relapse.
• When reinduction and intensification of chemo fails to respond local relapse, RT could be
used as consolidation or in conjuction with BMT.
• AML :
• AML sensitive to radiation; response is often apparent after 12–15 Gy.
• Consolidative therapy has been reported to be effective at 18 Gy;
• lesions that show incomplete response to chemotherapy may require 21–27 Gy focally.
• TBI as immunosuppressant for HSCT to eliminate residual lymphoblasts or
myeloblasts and to immunosuppress the host so that the donor marrow is
accepted.
Brain Tumor
• Low Grade Astrocytoma :
• 1st Surgery: GTR, excellent control, 90% long term DFS, neurological deficits
depends on location.
• 2nd Radiotherapy: adjuvant post Sub Total Resection, 82-87% 10 yr PFS, 90%
10 yr OS, for thalamic region 33-60% 10yr OS, beware radiation toxicity.
• 3rd Chemo: could be use to delay Radiotherapy concerning related radiation
toxicity (age below 5 yo, tumor location).
• Prognosis is related to age at diagnosis and degree of surgical
resection; older children usually enjoy more favorable outcome.
GTR is consistently linked to improved PFS
• Oligodendroglioma:
• 1st Surgery:
• Total surgical resection, 60% 10 yr OS
• Sub total resection, 25% 5 yr OS
• 2nd RT: adjuvant to Sub Total Resection; 62% 5 yr OS; 31% 10 yr
OS
• 3rd Chemo: associated with sufficient tumor reduction to
permit delayed GTR in tumors initially felt to be unresectable
• Malignant/High Grade Glioma
• Surgery:
• Anaplastic astrocytoma: >90% vs less aggressive resection  5 yr PFS 44% vs 22%
• Glioblastoma: >90% vs less aggressive resection  5 yr PFS 26% vs 4%
• Radiotherapy (after surgery):
• After Gross Total Resection (GTR): 3-5 yr EFS 45%
• After Sub Total Resection (STR): 3-5 yr PFS 5-20%
• Median Survival: 18-24 mo
• Chemo:
• Used subsequently with Surgery & Radiation
• No benefit of temozolomide in children as in adult malignant glioma
• Current trials in COG and the Pediatric Brain Tumor Consortium (PBTC) focus on the
addition of molecular targeting agents (a series of anti-angiogenic compounds
targeting VEGF and related angiogenesis pathways as well as EGFR, PDGF, and mTOR
inhibitors) administered concurrently or sequentially with irradiation
• Germ Cell Tumor
• Pure Germinoma (better prognosis):
• Radiotherapy has long been the standard sole treatment or an essential element of
treatment
• quite chemoresponsive; the use of combined chemotherapy and limited-volume and/or
limited-dose irradiation has been an alternative approach in treating these tumors
• Nongerminomatous Germ Cell Tumor (NGGCT):
• Radiotherapy is an important component of multimodality therapy for NGGCT
• irradiation alone has achieved disease control in only 20–45% of tumors, and combined-
modality therapy, also including chemotherapy and potential surgical resection, is
standard.
• Surgery:
• Biopsy for unclear tumor marker (AFP & bHCG)
• For tumor which not responding to chemo and radiotherapy
• Ventricle decompression, V-P Shunt, drain
• Endoscopic third ventriculostomy (ETV) is a particularly attractive, alternative method of
treating hydrocephalus by diverting CSF flow and obtaining a biopsy under direct
visualization.
• Radiotherapy:
• For pure germinomas, radiation therapy has been the major curative modality. 5 yr
DFS 90–95% with the use of irradiation alone (40-50 Gy)
• For NGGCTs, combined chemotherapy and irradiation is the standard.
• For NGGCTs, chemotherapy followed by CSI plus a boost to the primary site have
yielded long-term survival rates of 67– 74%
• BUT with some uncertainty regarding the appropriate radiation volume (local, whole
ventricle, whole brain, or craniospinal) relating to patients age and tumor location.
• RT Dose and volume depend on tumor response after chemo
• Chemo
• GCTs are chemosensitive, response rates approach 100% for germinomas, Disease
control 50%.
• Chemotherapy prior to RT given to reduce radiation dose (24-36 Gy) and volume so
the toxicities can be lowered and improving long-term functional outcomes
• For NGGCT Chemotherapy has become a standard component of therapy for these
tumors prior to irradiation.
• High-dose chemotherapy with stem cell rescue has shown promise for relapsed
GCTs.
• Combined-modality Therapy for NGGCT:
• Longterm disease control rates of 50–67%, potentially improved with the addition of
surgical resection or selected use of radiosurgical boost to the primary residual
tumor.
• Medulloblastoma
• Surgery  CranioSpinal Irradiation (with/without chemo concurrent)
 Chemo adjuvant
• Average Risk ( >3 yrs old, M0, near total <1.5cm2 / total resection )
• >80% 5 yr EFS & OS
• High Risk ( <3 yrs old, M123, >1.5cm2 tumor residual )
• 60-70% 5 yr EFS & OS

• Ependymomas
• Surgery + Irradiation
• 5 yr EFS & OS 69% & 80%
• Surgery + Chemo
• 5 yr EFS & OS 42% & 63 %
Lymphoma Hodgkin
• Treatment
• Chemo alone
• RT Alone (full dose)
• Chemo (low dose) + Involved Field RT (IFRT)(low dose)
• Early & Favorable : 10 yr OS 85-95%
• Advanced & Unfavorable : 10 yr OS 70-90%
• Patients with stage I, IIA, or IIIA HL were randomized in a study conducted by
the POG At a median follow-up of 8.25 years.
• 6 courses alternating MOPP/ABVD : 8 yr EFS 83%; OS 93.6%
• 4 courses MOPP/ABVD and IFRT (25.5 Gy) : 8 yr EFS 91%; 96.8%
• no significant differences in EFS or OS rates between either arm.
• In summary, numerous investigations have confirmed that chemotherapy
alone is an effective treatment approach for PHL
• Refractory & Relapsed Hodgkin Lymphoma

• Standard dose chemo ± RT

• RT alone
• Stem Cell
• High dose chemo ± RT (TBI, TLI), followed by stem cell support
(allogeneic or autologous); superior outcome, 3-5 yr OS
probability 25-80%
• Autologous bone marrow transplantation + IFRT (3 yr relapse
free 100% & OS 85 %); For patients not previously irradiated,
IFRT was associated with an improved freedom from relapse of
85% and OS of 93%
• Palliative therapy
Late effects of cancer treatment
Evaluation of Patients at Risk for Late Effects:
Late effects Chemo Radiation Surgery Management
Neurocognitive High dose IV MTX, IT >18 Gy Resection of CNS Psychoeducation
deficit MTX tumor assistance
Focal CNS necrosis IT or high dose IV >50 Gy ( >2Gy daily Tumor resection Steroid, debulking of
MTX, carmustine, fraction necrotic tissue
cisplatin
Vision loss Intraarterial >50 Gy (optic nerve, Tumor resection Visual aids
carmustine, cisplatin chiasm, occipital
lobe)
Ototoxicity Cisplatin, carboplatin >35 Gy (middle ear & Surgery, CSF shunting Speech therapy,
inner ear) hearing aid
Myelitis 45-50 Gy Spinal cord surgery Steroids, physical
therapy,
occupational therapy
GH deficiency >18 Gy to Hypophysis Tumor in hypophysis GH therapy, Delay
(HP) axis axis puberty with GnRH
agonist
ACTH deficiency >40 Gy to HP axis Tumor in HP axis Hydrocortisone
Precocious puberty >20 Gy to HP axis Tumor in HP axis GnRH agonist
(girl)
Gonadotropin >40 Gy to Tumor in Testosterone
deficiency (male) hypothalamic region hypothalamus replacement
Evaluation of Patients at Risk for Late Effects:
Late effects Chemo Radiation Surgery Management
Gonadotropin >40 Gy to Tumor in Hormone
deficiency (female) hypothalamic region hypothalamus replacement
Metabolic Steroids Refer to
syndrome endocrinology
Muscular >20 Gy (growing Muscle loss / Prevention: good
hypoplasia child) younger resection exercise program
children more
sensitive
Cardiomyopathy Anthracycline >300 >35 Gy, >20 Gy with Diuretics, digoxin,
mg/m2, high dose CTX Anthracycline afterload reduction,
bone marrow antiarrhythmics,
transplant, ifosfamide cardiac transplant,
etc
Pulmonary fibrosis Bleomycin, lomustine, Pulmonary RT 15-20 Consider pulmonary
carmustine, CPM, MTX, Gy, risk increases evaluation, steroid
mitomycin, vinca with dosage, larger therapy
alkaloids volume irradiated
and younger age
Ovarian failure Nitrogen mustard, 4-12 Gy, tolerance Oophorectomy, Hormone
cyclophosphamide, decreases with oophoropexy replacement
procarbazine, busulfan, increasing age (estrogen), referral to
melphalan, reproductive
dacarbazine, endocrinology, etc
carmustine, lomustine,
ifosfamide
Evaluation of Patients at Risk for Late Effects:
Late effects Chemo Radiation Surgery Management
Germ cell damage: Cyclophosphamide, 1-6 Gy Orchiectomy or Referral to
oligospermia & nitrogen mustard, surgical manipulation reproductive
azoospermia lomustine, endocrinology,
carmustine, infertility counseling,
procarbazine, anticipatory
ifosfamide, busulfan, guidance regarding
melphalan, germ cell damage
dacarbazine
Leydig cell damage: Cyclophosphamide, >24 Gy to testes Orchiectomy Testosterone
testosterone etoposide replacement,
deficiency anticipatory
guidance regarding
testosterone
deficiency
Bladder: fibrosis or Cyclophosphamide, >30 Gy Exercises to increase
hypoplasia (reduced ifosfamide prepubertal, >50 bladder capacity,
bladder capacity) Gy postpubertal surgical referral
Retina: infarction, >50 Gy Steroids
exudates,
hemorrhage, macular
edema
Xerostomia >40 Gy and >50% Encourage
(decreased salivary of gland must be meticulous oral
gland function) radiated hygiene, saliva
substitution etc
Anesthesia for Pediatric Radiotherapy
.... In a small number of patients in the infant to toddler age group of
1½ to 5 years of age, patient cooperation may be impossible to
obtain.... Complete immobility of the patient is absolutely essential
for the accuracy and success of treatment.... Sedation of the patient
becomes virtually a sine qua non.
-Harrison & Bennet (Radiotherapy without tears)
• Behavioral techniques to avoid anesthesia:
• music, cartoons, stories, videos, praise, stickers, toys, prizes
• Music therapists, psychologists, play therapists, social workers,
and RTT
• cheerful murals painted on the walls of the radiotherapy
waiting room, and decorating stabilization devices with
childfriendly themes
Goals for Ideal Anesthesia for Outpatient Pediatric Radiation Therapy:

• Patient immobility
• Rapid and smooth onset of effect with sedation, hypnosis, amnesia, and analgesia adequate for
nonpainful radiation therapy procedures, along with a sufficient degree of muscle relaxation
• Brief duration of action
• Painless administration
• Prompt recovery without postprocedure side effects but with residual analgesia and antiemetic
effects during recovery
• Minimal interference with eating, drinking, and playing
• Safety for repeated administration
• Low risk of tolerance to the anesthetic agents (tachyphylaxis)
• Maintenance of a patent airway in a variety of body positions
• Absence of side effects such as cardiovascular instability, respiratory depression, spontaneous
movements, and excitatory activity
• Cost-effectiveness
THE GROWING POPULATION OF SURVIVORS
• Provide the child with a functional cure, regaining or retaining the ability to function in
society without major handicaps and minimizing the need for a significant support.
• Survivors are at a higher risk of impaired pulmonary function, growth abnormalities,
endocrine dysfunction, obesity, physical limitations, infertility, cardiac problems, reduced
quality of life, depression, special educational needs, and second malignant neoplasms.
• Planning for adequate limb function, ambulation, and activities of daily living is crucial in
planning a course of treatment. Rehabilitation including physical, occupational, and
recreational therapy plays an important part in follow-up care. A comprehensive pediatric
cancer rehabilitation program requires people with expertise in prosthetics, orthoses,
ostomy care, gait training, and pain management.
• Attention to the child’s emotional status is also important. Preserving and nurturing a
sense of well-being on the part of the child and his or her family. The term “psychological
cure” refers to the ability to put cancer behind you and move on with life.
Conclusion
• Early detection and action  better cure and survival
• Multi-modality teamwork is a must, to achieve excellent
long term survival
• Psychosocial and medical rehabilitation needed for long-
term treatment sequele
• Research should continue to enhance curability and
reduce treatment side effect and improving quality of life

Tantangan Radioterapi Pediatrik
 Spektrum yang luas dari penyakit yang kompleks, dengan berbagai
komponen biologis nya serta etiology nya.
 Integrasi radioterapi yg optimal dan kreatif di dalam pengobatan
membutuhkan pemahaman yang mendalam tentang penyakit tsb serta
konsekuensi klinis yang dapat terjadi.
 Onkologi pediatrik cukup menakutkan bagi radiation oncoloist pd
umumnya, krn setiap pasien membuka cakrawala baru yg asing. Tidak
hanya sekedar terjun di dalam nya, melainkan harus sukses dan
berhasil.
 Risiko sangat tinggi, margin of error sangat tipis, sebagian besar kanker
pediatrik sangat “curable”, tp anak dapat cedera & hidup dalam waktu
yg lama dengan cacat.

Faktor2 yg mempengaruhi
 Semakin muda usia pasien, akan semakin sulit dan teliti (presisi) radioterapi yang
diberikan.

Kreatifitas tinggi

Fiksasi & Immobilisasi → pasien yg tdk kooperatif wajib Anestesi di saat simulasi dan setiap
radiasi.
 Tidak boleh ada perasaan traumatis/takut saat radiasi (why?)

Pendampingan oleh perawat/petugas yg berpengalaman dalam pediatrik, memberikan
motivasi serta reward bila perlu.

Radiasi se nyaman mungkin dengan Anestesi bila terpaksa.
 Prognosis dan efek samping terapi (yg tidak dapat dihindari)

Informed cosent yg kuat terkait risk & benefit
 Follow up

yang teratur dan teliti

penanganan tumbuh kembang (fisik, mental, neuro-psikiatri)
• The child with cancer is discomforting to the physician.
However, this discomfort should not paralyze the
physician with indecision or doubt about a course of
therapy. It is reasonable for the physician to be angry and
distressed about the child with cancer.
Terima
Kasih
• Reference
1. EC Halperin, LS Constine, NJ Tarbell, LE Kun. Pediatric Radiation Oncology. 5 th ed. Philadelphia:
Lippincott Williams & Wilkins; 2011.
2. CA Perez, LW Brady, EC Halperin, DE Wazer. Principles and Practice of Radiation Oncology. 6 th ed.
Philadelphia: Lippincott Williams & Wilkins; 2013.