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MANAGEMENT OF NASOPHARYNGEAL ... MANAGEMENT OF NASOPHARYNGEAL CARCINOMA IN CHILDREN RELATIVE FREQUENCIES OF MAJOR TUMOUR TYPES IARC 2005 NASOPHARYNGEAL CARCINOMA Common: Southern China

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  • 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 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

    47.2 52

    32.1

    55.4

    41.9

    57.4

    0

    10

    20

    30

    40

    50

    60

    D o s e i n 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