H&N cancer: CHUM-Hpital Notre-Dame experience Denis Soulires, - - PowerPoint PPT Presentation

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H&N cancer: CHUM-Hpital Notre-Dame experience Denis Soulires, MD, MSc Hematologist and Medical oncologist Chemoradiation therapy Objectives: Increase in survival Better local control Decrease occurrence of distant

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H&N cancer: CHUM-Hôpital Notre-Dame experience

Denis Soulières, MD, MSc Hematologist and Medical oncologist

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Chemoradiation therapy

 Objectives:

– Increase in survival

Better local control
Decrease occurrence of distant metastasis

– Organ preservation

Larynx
Oropharynx

– Quality of life

Tolerability of the proposed therapy

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Therapeutic schemes:

 Primary systemic therapy followed by

radiation therapy

 Concomitant chemoradiation therapy

Primary
Post-op

 Adjuvant chemotherapy

Post-radiation
Post surgery and radiation therapy

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Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional

treatment for head and neck squamous- cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer.

Lancet 2000;355(9208):949-55.

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Pignon et al.

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Meta-analysis: Chemotherapy Pignon

CT !Risk ! p !Benefit Timing !Reduction ! value ! at 5y!

Overall survival

Adjuvant ! 2% !N.S 1%! Induction ! 5% !N.S 2%! Concomitant !19% !< 0.0001 8% ! 11% !< 0.0001 4% ! Total !!

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Updated Pignon meta-analysis

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Update of MAHN-NC

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Experience Notre-Dame

 Median age: 57 yo  245 (77%) M and 73 (23%) F  Stage III 48 (15%) and stage IV 270 (85%)  Site:

– 67% oropharynx – 13% larynx – 7% hypopharynx – 18% autres

 Median follow-up 19 mois

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Experience Notre-Dame

 Carbo/5-FU q 3 sem: 178 (56%)  CDDP q 3 sem: 86 (27%)  Carbo die: 42 (13%)  CDDP die : 6 (2%)  CDDP q 1sem: 4 (2%)

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Experience Notre-Dame

 Surgery for any residual

disease detected clinically

r radiologically (primary

site and/or nodes)

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Experience Notre-Dame

 Tx: 14 (4)%  T1: 42 (13%)  T2: 63 (20%)  T3: 104 (33%)  T4: 95 (30%)

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Experience Notre-Dame

 N0: 33 (10%)  N1: 43 (14%)  N2: 190 (60%)  N3: 52 (16%)

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Overall survival !

OS at 2y: 70%! OS at 3y: 63%! !

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Loco-regional control !

LRC at 2y: 88%! LRC at 3y: 85%! !

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Distant DFS

Distant metastatic disease: At 2y: 13% At 3y: 16%

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Influence on the type of chemotherapy

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OS based on the type of chemoRx !

carbo + 5FU or cisplatin q 3w vs others !

*p value < 0,0001  !

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Distant DFS according to type of chemotherapy

!

carbo + 5FU or cisplatin q 3 w vs others !

*p value < 0,0001 

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The effect of HPV: HND experience

 HPV prevalence and prognostic value in a

prospective cohort of 255 patients with locally advanced squamous cell carcinoma of the head and neck treated with chemoradiation therapy

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Introduction and methods

 Background and objectives

– HPV prevalence in HNSCC increasing over the past few decades

Clinically and molecularly different subset

– Improved prognosis for HPV+ cancers – Most data derived from trials with different treatment options or small heterogeneous cohorts, and often collected retrospectively. – Objective: to determine HPV prevalence and effects of tumour HPV status on treatment response and survival outcomes amongst HNSCC uniformly treated patients

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Methods

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Prospective data on efficacy and toxicity available for 560 patients treated with concomitant CRT



270 fixed and paraffin embedded specimens; sufficient tissue for DNA extraction in 255 samples



Presence of HPV DNA in samples determined using the Roche Linear Array detection method (LA-HPV)

Coutlee, F., et al., Enhanced detection and typing of human

papillomavirus (HPV) DNA in anogenital samples with PGMY primers and the Linear array HPV genotyping test. J Clin Microbiol, 2006. 44(6): p. 1998-2006



Statistical analysis: – Kaplan-Meier survival curves – Fisher’s test for categorical data – Log-Rank statistics for failure times

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Results: Patient characteristics

Patient Characteristic

Number %

HPV + 175 68.63

31.37 Age (years) Median 57.00 Range 25.25-78.72 TNM Stage I II 2 0.78 III 35 13.73 IVa 166 65.10 IVb 44 17.25 Recurrence 8 3.74 KPS 60 1 0.47 70 4 1.89 80 41 19.34 90 148 69.81 100 18 8.49 Chemotherapy

Daily carboplatin or cisplatin

27 10.63

Daily Carboplatin + 5FU

146 57.48

Cisplatin q 1 week or q 3 weeks

81 31.89 Radiotherapy

Conventional

221 86.66

IMRT

34 13.33

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Results:

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Results: OS for oropharynx

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Results

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Results:

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Discussion:

 Our results confirm the HPV is a pronostic

factor for OS, DFS and LCR in locally advanced HNSCC

– Specifically for patients treated with chemoradiation therapy

 Our data neither confirm nor infirm that HPV-

related HNSCC can be treated with a less stringent therapy

– The development of chemoradiation therapy in cervical cancer seems to argue for more intensive therapy

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Perspectives:

 HPV genotyping should be a stratification

factor for all clinical trials including HNSCC cases

 Interaction assays should be incorporated in

all future HNSCC trials – Differenciate the pronostic and predictive value of HPVbased on different therapies

 Different biology of HPV disease argues for

different agents and separate trials

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Perspectives:

 Large cohorts of patients treated with

chemoradiation are required to establish:

– Prognostic factors – Predictive factors – Revision of staging based on new therapies