ROLE OF RADIOTHERAPY

in

Nasopharyngeal carcinoma

Dyah E, Lulus, Ulinta, Yoke

NPC differs from other H & N cancer:

• Epidemiology

• Pathology

3 histological types (W.H.O.)

Type I – Keratinizing SCC

Type II – Nonkeratinizing

Differentiated Carcinoma

Type III – Nonkeratinizing

Undifferentiated

Carcinoma

• proven role of EBV (1966)

• Diagnostic approach

• Treatment & Outcome

Introduction

RT as the mainstay

• Difficult surgical approach

• Sensitive to radiotherapy

Three Major Issues of the NPC

• How to improve the local control especially

for T3 and T4 patients

• How to reduce the post-irradiation late

sequelae

• How to reduce the ratio of distant

metastasis

Pattern of failure

T1-2 N0-1: good outcome

T3-4 N0-1: local failure dominant

T1-2 N2-3: distant failure dominant

T3-4 N2-3: bothEfficacy of RT

• Control rate

T1/T2: 75-90%

T3/T4: 50-75%

N0/N1: 90%

N2/N3: 70%

• Incorporate chemotherapy to RT

GOAL OF RT

• Maximize probality of tumor

eradication.

• Minimize probality of injury

to surrounding normal

tissue

RT FOR HEAD & NECK EXTREMELY

COMPLEX

I. TUMOR

• Very close proximing of tumor

& critical structure

• Total dose delivery limited by

tolerance of N tissue

II. ANATOMY

Varying Contour & TissueHeterogeneities

Air Sinuses

III. PATIENT

Compromised tolerance to Tx

- Poor nutritional status

and weight loss

- Inadequate oral intake

- Treatment induced

mucositis.

DIFFICULTY IN RT FOR H & N CANCER

IV.

TOLERANCE

DOSE

Source : PK Julka. Dept of Radiotherapy and Oncology AIIMS . New Delhi

Highly conformal radiation technique, such as IMRT

offerthe potential to reduce the spectrum side effects

associated with RT by decreasing the volume of

normal tissue receiving RT

3 DCRT utilizes CT-based treatment planning with dosimetric software to create

composite treatment plans. Fusion of planning CT with MRI is extremely helpful in

assisting with target definition

2D High dose surrounding normal tissue

IMRT

Improves precision/accuracy

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RT TECHNIQUE

3DCRT VMAT

Advanced Techniques : SRS and SRT

- Delivery of high dose of radiation in a single fraction

to small and precisely delineated intracranial lession

Stereotactic RadioSurgery (SRS)

- Delivery of high dose of radiation in a multiple

fraction to small and precisely delineated

intracranial lession

Stereotactic RadioTherapy (SRT)

Heavy particle RT ( PROTON, NEUTRON ect)

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RT TECHNIQUE

BRACHYTHERAPY

TOMOTHERAPY

STRATEGY TO IMPROVE RT

BIOLOGICAL APPROACH

DRUG COMBINATION

FRACTIONATION

HIGH LET

Improvement of

radiosensitivity

PHYSICAL APPROACH

CT based RTPS

3 D, IMRT, VMAT

STEREOTACTIC

Improvement of

dose distribution

ADVANCEMENT OF RT

LOCAL CONTROL SURVIVAL

QOL

CHEMO-RADIASI

29 AUGUST 2020

Randomized clinical trials on CRT for NPC

study

INT 0099a)

Chan’sb)

Taiwanc)

Singaporea)

Hongkonga)

no

147

350

284

221

348

CRT arm

78%

70%*

81%

80%

78%

RT arm

47%

59%*

70%

65%

78%

P-VALUE

0,001

0,049

0,002

0,006

NS

3 y OS

a) RT+ Cisp Cisp/5FU

b) RT+Cisp

c) RT+Cisp/5FU(IJROB 2008, Chen Y. et al )

29 AUGUST 2020

INTERNATIONAL MULTICENTER CLINICAL TRIAL OF NPC

FORUM for NUCLEAR COOPERATION in ASIA

( FNCA )

Phase II

29 AUGUST 2020

N0 N1 N2 N3

T1

T2

T3

T4

NPC-I

NPC-II

RT+ weekly Cisplatin

Adjuvant (Cis+5FU

N0 N1 N2 N3

T1

T2

T3

T4

NPC-I

NPC-II

RT+ weekly Cisplatin

(without adjuvant chemo)

Protocol : NPC- IIProtocol : NPC - I

(Cispl 30 mg/m2)(Cispl 30 mg/m2 )

(Cispl 80 mg/m2 & 5-FU: 1000

mg/m2/dayx4days )

Weeks 11, 15,19

(6x)(6x)

29 AUGUST 2020

TUMOR RESPONSE

Study Group

INT 0099

Singapore

Hongkong

Chan’s

FNCA (NPC-II)

FNCA (NPC-I )

CT/MRI

Yes

Yes

yes

yes

no

NR

TIMING

Every 2 Mo

6 Mo

6 Mo

6 Mo

6 Mo

6 Mo

CRT

36%

97%

98%

83%

95%

94%

RT

49%

97%

99%

71%

Complete Response

29 AUGUST 2020

TOXICITIES IN CONCURRENT CRT ARM

Study Group

INT 0099

Singapore

Hongkong

40mg/m2/w

FNCA (NPC-II)

FNCA (NPC-I )

Cisplatin

100mg/m2/3w

100mg/m2/3w

100mg/m2/3w

Chan’s

30mg/m2/w

30mg/m2/w

mucositis

37%

48%

62%

49%

13%

35%

N/V

14%

NR

19%

12%

2 %

5%

Leukopenia

29%

NR

32%

13%

4%

4%

TOXICITIES > grade 3

29 AUGUST 2020

TARGETED THERAPY + RT

Phase II trial 0f Recombinant Humanised Anti- human EGFR Monoclonal Antibody Nimotuzumab in Patients with locally advanced NPC

(Xu Guozhen, Gao Lie)

The CR rate in Px treated with combined tx was significantly higher than that in px receiving monotherapy.

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CT SIMULATOR

TPS (Treatment Planning System)

Radiation Treatment

RT PROCEDURE

(EBRT)

OUT PATIENT

(CLINIC)

Depend on :

• Total dose.

• Total duration of treatment

• Dose per fraction.

• Total number of fraction

• Interval between fraction

• Radiation volume.

TOXICITY

29 AUGUST 2020

ORAL COMPLICATION OF RT

Dysphagia 65 – 100 %

Xerostomia 78 – 95%

Dysgeusia ( change taste) 90 %

mucositis/ stomatitis 45 – 93 %

Pain 75 – 85 %

Chewing/ eating difficulties 70 %

( Brizel.DM. et al.J.Clin.Oncol.2000;18:3339-3345. Scully.C.et al. Head &Neck.2004;26:77-84.Berk.LB.et al.

2005;3:191-200 )

Increase acute toxicity with combined RT + CT

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29 AUGUST 2020

SUMMARY

The Radiation management

Side effect : recent technique

Multidisipline approach

individual. Management NPC

Perfect balance

Top skill

Multidisipline Approach :

ENT

Radiologist

Patologist

Radiation Oncologist

Hemato Oncologist

Nutrition

RT TEAM

• RADIATION ONCOLOGIST ( RO )

• MEDICAL PHYCISIST ( MP )

• DOSIMETRIST

• RADIOTHERAPY TECHNOLOGIST ( RTT)

• NURSE ONCOLOGIST

TEAM WORK

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