Post on 29-Dec-2019
MANAGEMENT OF NASOPHARYNGEAL
CARCINOMA IN CHILDREN
RELATIVE FREQUENCIES OF MAJOR TUMOUR TYPES
IARC 2005
NASOPHARYNGEAL CARCINOMA
Common: Southern China Southeast Asia Mediterranean Alaska
Rare: Japan Europe North America
0 5 10 15 20
China
UK
USA
India
Turkey
Tunisia
Uganda
Median Age: 13Years (Bimodal Peak:10-20yrs & 40-60yrs)
Male: Female: 1.8:1
Cancer 1978
IJROBP 1989
IJROBP 1990
IJROBP 2004
0.1% of all Cancers at the TMH
1.5% of all Pediatric Malignancies at TMH (Approx 12 per year)
RADIOTHERAPY
Primary: 66 – 70 Gy
Neck: 50 Gy/ 25 fr
CHEMOTHERAPY
Neoadjuvant
Concomittant
Adjuvant
STANDARD MANAGEMENT
RADIATION THERAPY
RADIOTHERAPY PORTALS
Author n Dose Locoregional
Control Survival
Jenkin R
17 <47 Gy RR 29% 58%
20 48–55 Gy RR 5% 66%
40 56–63 Gy RR 28% 55%
27 >63 Gy RR 22% 41%
Ayan I 23 50–72 Gy LRCR 74% 46%
Serin M 32 18–70 Gy LRCR 61% 42%
Uzel O 20 60–70 Gy LRCR 74% 75%
Sahraoui S 30 60–70 Gy NA 38%
Wolden SL 13 54–72 Gy LRCR 65% 36%
Sham J 71 45–66 Gy LRCR 34% 24/71 NED
Laskar S 81 56-66 Gy 45% 54%
RADICAL RADIOTHERAPY (NON-IMRT STUDIES)
Ayan, Lancet Oncol. 2003 Laskar, IJROBP 2004
RESULTS WITH COMBINED CT + RT
Ayan, Lancet Oncol. 2003
Laskar et al, IJROBP 2004
RESULTS & PROGNOSTIC FACTORS
DFS: 45% OS: 54%
Median FU: 50 months
Laskar et al, IJROBP 2004
Prognostic factors cont….
Laskar et al, IJROBP 2004
PATTERNS OF FAILURE
Laskar et al, IJROBP 2004
Laskar et al, IJROBP 2004
INFERENCES
• T & N Stage impact outcome
• CT+RT superior to definitive RT
• Good responders to neoadjuvant CT – Superior outcome
• RT dose >60 Gy – Superior results
• CT+RT result in good locoregional control
• Distant failure is frequent
Radiotherapy & Oncology 2006
RESULTS
Radiotherapy & Oncology 2006
PROGNOSTIC FACTORS
Radiotherapy & Oncology 2006
Radiotherapy & Oncology 2006
PTV70 (70.2Gy/ 33# @ 2.12Gy/#)
PTV59.4 (59.4Gy/ 33# 1.8Gy/#)
PTV52.8 (54.8Gy/ 33# 1.6Gy/#)
PTV70
PTV59.4
PTV54.8
IMRT
IMRT CONVENTIONAL RT
DOSIMETRIC COMPARISION OF TREATMENT PLANS
Laskar, IJROBP Sept 2008
42.8
53.4
47.252
32.1
55.4
41.9
57.4
0
10
20
30
40
50
60
Dose in G
y
Spinal Cord Brain stem Contralateral
Parotid
Ipsilateral
Parotid
IMRT
Conventional RT
COMPARATIVE DVH FOR CRITICAL ORGANS
Laskar, IJROBP Sept 2008
Laskar, IJROBP Sept 2008
TIME TO DEVELOPMENT OF GRADE II TOXICITY
Laskar, IJROBP Sept 2008
COMPLICATIONS
TREATMENT COMPLICATIONS
ACUTE LATE
CHEMOTHERAPY Haematological
Nausea/ Vomiting
Alopecia
Pulmonary
Neuropathy
Neuropathy
Autotoxicity
Second Cancers
RADIOTHERAPY Dermatitis
Mucositis
Hoarseness of Voice
Dysphagia
Subcutaneous Fibrosis
Xerostomia
Impaired Taste
Musculo-Skeletal
Hormonal- Pituitary,Thyroid
Visual Injuries
Autotoxocity
Dental Carries
Second Cancers
10 years post treatment
PHYSICAL & BIOLOGICAL OPTIMIZATION
OF THERAPY IN CHILDREN
Complete Pretreatment Diagnostic & Staging Evaluation
Study Related Investigations & Documentations
Audiogram, Ophthalmologic Eval., Sailometry, Baseline QOL et.
Neo-Adjuvant Chemotherapy
(BMP X 2#)
Response Evaluation / Study Related Investigations
Intensity Modulated Radiation Therapy (IMRT)
+
Concomitant Cisplatin x 6#
Response Evaluation / Study Related Investigations
IMRT + Multiagent Chemo:
Improve Disease Control
Decrease Treatment Related Acute & Late Toxicity
Improve Quality of Life
Biological Studies:
EBV DNA: Prognostic marker, Tumor Monitoring
MDR Gene: Identify Probable Non-responders
EGFR studies: Targeted Therapy
Radiobiological Studies:
Identify Radiosensitive Tumors (Reduce RT Dose)
DNA Damage: Correlate with 2nd Malignancies
HELICAL TOMOTHERAPY
Significant Improvement in Normal Tissue Sparing
PHOTON IMRT PROTON IMRT
AREAS FOR RESEARCH
Pathology Genetic Signatures
Prognostic Markers
Pre-treatment sensitivity testing
Chemotherapy Sequence of Therapy
Neoadjuvant
Concurrent
Adjuvant
New Drugs
Reduced toxicity
Radiotherapy Response based Radiation Dose
Redn of Normal Tissue Toxicity (Tomo, Protons)
Targeted Therapy Anti EGFR
Follow up Strategies EBV Viral DNA levels