Download pdf - MANAGEMENT OF NASOPHARYNGEAL …...MANAGEMENT OF NASOPHARYNGEAL CARCINOMA IN CHILDREN RELATIVE FREQUENCIES OF MAJOR TUMOUR TYPES IARC 2005 NASOPHARYNGEAL CARCINOMA Common: Southern

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


Prognostic factors cont….


PATTERNS OF FAILURE



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


PROGNOSTIC FACTORS



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



TIME TO DEVELOPMENT OF GRADE II TOXICITY


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