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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
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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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11
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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20
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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
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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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34
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35
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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 38Do not duplica
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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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