Do not duplicate or distribute without permission from ... · T1N0M0 > RT T1N1-3, T2-T4 any N 1. Multimodality clinical trial 2. Concurrent CT/RT > Adjuvant CT 3. CT/RT (category

NPC

Lisa Licitra

H&N Medical Oncology Dept

Istituto Nazionale dei Tumori

& University of Milan

ItalyDo not duplica

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Former TYPE 1 Keratinizing squamous cell carcinoma (8071/3)

Former TYPE 2 Non keratinizing carcinomas (8072-3/3)

Differentiated non keratinizing carcinoma (8072-3/3)

Undifferentiated carcinoma (undifferentiated carcinoma of

nasopharyngeal type) (8020/3)

Former TYPE 3 Basaloid squamous cell carcinoma (8083/3)

Histological types WHO

25%

60%

12%

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EBV genomic variations are affected by: -geographic distributions, -environmentalinfluences-disease subtypes-phase of EBV latency

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NATURAL HISTORYGenetic, EBV latent infection, environmental carcinogenesis

Inherited (germline mut + EBV), endemic (gene polymorph + EBV) , sporadic(EBV + carcinogens)

Salted fish exp early life exposure, smoking

Familial cluster

M > F

40-60 peak age

Survival declining in EU!

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Prognostic factors

◼ Keratynisation

◼ TNM (supraclavicular nodes, masticatory space, T1

and T3)

◼ Tumor volume

◼ Gender F > M

◼ Age only in M

◼ QOL

◼ BMI

◼ IMRT

◼ Molecular: EGFR hx, p53 hx, PI3KCA, ERBB2, ERBB3

mut, miRNA, gene signature12/12/2018 6

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EBV-DNA testing

7

Screening for early NPC

Prognosis

Risk stratification for treatment

Disease surveillanceDo not duplica

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- OS according to EBV DNA value

1 week post treatmentPre-treatment value

Prognostic/Predictive Factors

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2013

Plasma: DNA was extracted and EBV DNA copy number was determined by real-time quantitative PCR (BamHI-W primer/probe)Do not duplica

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Guidelines for delineation

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NCCN Guidelines 2018

12/12/2018 12

◼ T1N0M0 > RT

◼ T1N1-3, T2-T4 any N

1. Multimodality clinical trial

2. Concurrent CT/RT > Adjuvant CT

3. CT/RT (category 2B)

4. Induction > CT/RT (category 3b)

◼ M1

1. Trial

2. CT/RT

3. CT

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JNCI,2011Do not duplicate or d

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12/12/2018 15

2018

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12/12/2018 18Do not duplica

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12/12/2018 21Do not duplica

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12/12/2018 22Do not duplica

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12/12/2018 23Do not duplica

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Hong Kong NPC Study Group 0502 Trial <br />(NCT00370890)

Presented By Anthony Chan at 2017 ASCO Annual Meeting

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Primary endpoint: Relapse free survival

Presented By Anthony Chan at 2017 ASCO Annual Meeting

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Overall survival in EBV DNA screening population

UICC stage

Post-RT plasma EBV DNA level

a) Post-RT plasma EBV DNA undetectable (=0 copy/ml)

b) Post-RT plasma EBV DNA detectable (>0 copy/ml)

IIB

III

IVAB

IIB

IIB

III

III

IVAB

IVAB

0

1-49

50-499

≥500

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Pts < 60 yrs

Excluded T3-T4N0

TPF at reduced doses (60-60-600)

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12/12/2018 28Do not duplica

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12/12/2018 29Do not duplica

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Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiotherapy (NCRT+CCRT) Versus CCRT Alone in Locoregionally Advanced Nasopharyngeal Carcinoma

Presented By Ming-Yuan Chen at 2017 ASCO Annual Meeting

Excluded T3N0, N1 Do not duplicate or d

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Efficacy analysis

Presented By Ming-Yuan Chen at 2017 ASCO Annual Meeting

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Efficacy analysis

Presented By Ming-Yuan Chen at 2017 ASCO Annual Meeting

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12/12/2018 36

CCR 2018

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Metastatic disease

◼ CDDP based RR 63-75%

◼ CDDP + Gem first line SOC

◼ Other active drugs: Taxanes, IFO, FU,

capecitabine,vinorelbine, gemcitabine , MTX, EDX,

cetuximab (11%)

◼ Non active drugs: TKI

◼ Immunotherapy: CTL, to disrupt EBV cell latency

(azactidine..), Nivo: 20% RR, PFS @1yr 19%

◼ Oligometastatic disease

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12/12/2018 39

2018

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Conclusions

◼Rare disease

◼CT is beneficial in NPC

◼Refinement of pts selection for

neoadjuvant/adjuvant (?) CT based on

prognostic factors and biology

◼Biological agents

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Sinonasal

Cancers

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FACTS in EUIncidence

n/100.000

Survival @ 5 yrs

Epithelial nasal and

sinonasal cavity cancers

<1

SCC 50%

Lymphoepithelial 27%

SNUC 34%

ITAC 50%

Salivary gland tumor

types

69%

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WHO 2017Keratinising SCC

Non keratinising SCC

Spindle cell SCC

Lymphoepithelial

SNUC

NUT carcinoma

Neuroendocrine

Small cell neuroendocrine

Large cell neuroendocrine

Adenocarcinomas

ITAC

Non ITAC

TeratocarcinosarcomaDo not duplica

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WHO 2017

• Sarcomas

• 12 subtypes

• Neuroectodermal tumors

• Ewing

• ONB (Hyams grading)

• MMDo not duplicate or d

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New described

epithelial entities• NUT midline carcinoma (NMC):

cromosome rearrangement

NUT/BRD4 + variants (NUT1

protein in IHC)

• HPV related carcinoma with

adenoid cystic like features (HPV

33)

• SMARCB1 (INI-1) deficient

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Am J Surg Pathol 2017Do not duplica

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2018

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Cancer 2017

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2018

54 pts

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Which chemotherapy?

• Maximise localregional and distant sites effect

• Histotype driven

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Response to

induction CT

is a strong

prognostic factor

Median survival:

CR → 21+ months

PR → 13.5 months

NR → 3 months

Hanna 2010

Licitra 2003

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Bossi Cancer Treat Reviews 2015Do not duplica

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Turri Zanoni Oral Oncol 2017Do not duplicate or d

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First evidence: TP53 predict pCR to induction chemotherapy

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Functional p53 determinants of pCR

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Head and Neck 2016

SCC

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Multidisciplinary approach for poor prognosis sinonasal tumors:

Phase II study of chemotherapy, surgery, photon and heavy ion radiotherapy

integration for more effective and less toxic treatment in

operable and inoperable patients

SINTART1 (OPERABLE PATIENTS)

Study design:

Ph II, single-arm, open-label, multicenter studies

SINTART2 (INOPERABLE PATIENTS)

Study design:RC/RP >80%:

heavy ion based RT+ CT

no RC or RP <80%:

Surgery + Heavy ion based RT+CT

histology-driven CThistology-driven CT

heavy ion based

RT+ CT

AJCC stage: II-III-IVa

AJCC stage: Tb4

Sample size: 40 patients

Sample size: 25 patients

Primary endpoint: 5-yr PFS from 40 to 65%

Primary endpoint: 5-yr PFS

from 14% to 40%

Protocol: SINTART1 // SINTART2Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano PI: Dott.ssa Lisa Licitra

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Conclusions

• WHO classification

• Multimodal therapeutic approach that

includes surgery, radiation and histotype

driven chemotherapy

• Biology to be exploited

• Multinational collaborationsDo not duplicate or d

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