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Nasopharyngeal Carcinoma: Management of localised disease

Dr Joseph Wee FRCRNational Cancer Centre SingaporeDuke-NUS Medical School, Singapore

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• “I have no conflicts of interest to disclose.”

Disclosure

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• Diagnostic work up• Staging• Radiotherapy• Follow up• Role of chemotherapy

Lecture Outline

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• Naso-endoscope and Biopsy• Staging

– MRI– CT PNS, thorax, abdomen and Bone Scan or PET-CT

• Bloods– FBC, u/e/Cr, LFT– EBV DNA– Hepatitis B screening– ? LDH, CRP

• Planning CT

Diagnostic Workup

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Staging – 7th edition

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Staging – 8th edition

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Staging – 8th edition

Lydiatt et al, CA 2017

Pan et al, Cancer 2016

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Staging – 8th edition

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Staging – 8th edition

Pan et al, Cancer 2016

Lydiatt et al, CA 2017

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• Diagnostic work up• Staging• Radiotherapy• Follow up• Role of chemotherapy

Lecture Outline

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RT - Planning CT

Lee et al, R&O 2018

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IMRT

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IMRT – Target Delineation - CTVp

IMRT – Target Delineation - CTVp

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IMRT – Target Delineation - CTVn

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IMRT – Target Delineation - CTVn

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IMRT – Target Delineation - CTVn

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IMRT – Target Delineation - OAR

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IMRT – Target Delineation - OAR

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• 70Gy in 33-35 fractions– Boost

• ?improve local control in 2D era (9% per Gy)• Brachytherapy, stereotactic boost• Risks of neurovascular complications

– IMRT era • Simultaneous integrated boost (SIB)

Total dose of RT

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IMRT Outcomes

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T4 failures

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GTV underdosing

GTV <66.5Gy > 3.4cc

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Marginal failures

70Gy to post NACT GTV64Gy to disappeared GTV

No survival detrimentBetter toxicity profile

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GTVp

GTVp > 48cc

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Late Toxicities

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NACT to reduce late toxicities

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How to avoid TLN

Two dosimetric features (D0.5cc and D10), is significantlyassociated with TLN status (P < .001)

rV40 < 10% or aV40 < 5cc

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TLN – genetic susceptibility

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Dysphagia

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Hippocampus sparing RT

RTOG Atlas

Radiation-induced neurocognitive function decline

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• Proton therapy– Kills less circulating T cells

Proton Therapy

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Follow up EBV DNA

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Salvage Surgery

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Endoscopic Nasopharyngectomy

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OS LRFS DMFS Gr 5 toxicity5 year 41% 72% 85% 33%

Salvage Re-RT

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Selecting patients for re-RT

https://prancis.medlever.com/

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Carbon ion for recurrent NPC

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• Diagnostic work up• Staging• Radiotherapy• Follow up• Role of chemotherapy

Lecture Outline

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• Early Stage – Stage 1, 2

Role of Chemotherapy : Can we individualize?

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T1 – Good local and Distant control

Oral Oncology 2018

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T2 - distant control

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T2 - distant control

Limited to those with N1 disease

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Benefit is Distant Control and not Loco-regional Control

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LN > 3 cmEBV > 4000 copies

Summary (1) – Early Stage Tumours

• T1N0-1 (LN<3cm) - IMRT• T2N0-1 (LN<3cm) - IMRT• T1-2N1 (LN>3cm, EBV>4000) - ddp-IMRT

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Standard of Care: Stage 3, 4

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2 trials – results expected very soon

• HK 0501– Al-Sarraf vs Reverse Al-Sarraf

• SYSUCC– Induction Cis-Gem Cis-IMRT vs Cis-IMRT

Food for thought #2

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• HK 0501– Induction is superior to Adjuvant

• SYSUCC– Induction is superior to CCRT

• When than can you omit Induction?

• Cis-Gem; Cis-Xeloda; Cis-5FU or TPF

• ?? Must it be ddp-RT – or should we be doing trials looking at ?5FU-RT or ?cyclo-RT

Scenario : If both trials are positive

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Thank you