Progress in Mesothelioma Progress in Mesothelioma Michael R. - - PowerPoint PPT Presentation

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Progress in Mesothelioma Progress in Mesothelioma Michael R. - - PowerPoint PPT Presentation

Apr 27, 2023 579 likes •908 views

Progress in Mesothelioma Progress in Mesothelioma Michael R. Johnston, MD, FRCSC Professor of Surgery, Dalhousie University Adjunct Professor of Surgery, University of Toronto Affiliate Scientist, Ontario Cancer Institute Mesothelioma Research

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SLIDE 1

Progress in Mesothelioma Progress in Mesothelioma

Michael R. Johnston, MD, FRCSC

Professor of Surgery, Dalhousie University Adjunct Professor of Surgery, University of Toronto Affiliate Scientist, Ontario Cancer Institute

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SLIDE 2

Mesothelioma Research Program Mesothelioma Research Program Mesothelioma Research Program Mesothelioma Research Program

  • Early Detection Study

– LDCT scan, questionnaire, biomarkers, spirometry

  • Treatment Protocols

– Trimodality therapy Trimodality therapy – Neo-adjuvant IMRT – Advanced disease chemo studies

B i R h S di

  • Basic Research Studies

– Genetic profiling of tumours – Immunomodulation in mesothelioma – Screening new therapies

  • Epidemiology Studies

A b t l t d l di – Asbestos related lung disease

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SLIDE 3

Mesothelioma Research Program Mesothelioma Research Program Mesothelioma Research Program Mesothelioma Research Program

Michael R. Johnston, MD Thoracic Surgeon Heidi Roberts, MD Radiologist Heidi Roberts, MD Radiologist Marc de Perrot, MD Thoracic Surgeon Ming Tsao, MD Pathologist R F ld MD M di l O l i t Ron Feld, MD Medical Oncologist Brenda O’Sullivan Coordinator Li Zhang, PhD Immunologist Masaki Anraku, MD Thoracic Oncology Fellow John Cho, MD Radiation Oncologist Geofrey Liu, MD, PhD Molecular Epidemiologist Martin Tammamagi, PhD Epidemiologist Demetris Patsios, MD Radiologist Gregory Pond Statistician Gregory Pond Statistician Albert Ebidia Database support

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SLIDE 4

Survival by Stage in Adjuvant Trials Survival by Stage in Adjuvant Trials

Brigham (Sugarbaker) Memorial (Rusch)

EPP+chemo+rads+chemo EPP+rads

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SLIDE 5

“Early” Mesothelioma “Early” Mesothelioma Early Mesothelioma Early Mesothelioma

21 year old student

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SLIDE 6
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SLIDE 7

First Sites of Relapse after EPP and 54 Gy Rad Tx Rad Tx

Locoregional only 2 Distant only 30 y Locoregional and distant 5 Locoregional 7 Pleural 3 Pleural 3 Nodal 4 Distant 30 P it l 17 Peritoneal 17 Intralateral visceral 5 Contralateral pleural 13 Contralateral lung 8 Bone 7 Central nervous system Other 5 Some patients had more than one site of recurrent disease at relapse. p p

  • Rusch. J Thorac Cardiovasc Surg 2001
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SLIDE 8

Treatment Protocol Treatment Protocol

pathology review pleurodesis

Malignant pleural Mesothelioma

pathology review pleurodesis

Ci l ti b d h th

staging re-stage

Cisplatin based chemotherapy Hemithoracic radiation Extrapleural pneumonectomy

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SLIDE 9

Chemotherapy Toxicities (N=19) Chemotherapy Toxicities (N=19)

14 10 12

patients

6 8

mber of p

2 4

Num No compl. Nausea Paresth. Fever PE

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SLIDE 10

Extrapleural Pneumonectomy Extrapleural Pneumonectomy Extrapleural Pneumonectomy Extrapleural Pneumonectomy

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SLIDE 11

Major Post operative Complications Major Post-operative Complications

57 consecutive patients undergoing EPP

Technical* Deaths ARDS/pneumonia BPF/Empyema Esophageal perf Atrial Fib Cardiac arrest Pulm emboli 5 10 15 20 25 30 35 40 Total Complic Atrial Fib % of patients % of patients

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SLIDE 12

Risk Factors for Major Complications Risk Factors for Major Complications

p-value* p-value Univariate Multivariate

  • Right sided EPP

0.01 0.02

  • RBC transf >4 units

0.03 0.03

  • Age (> 60 yo)

0.06 0.1

  • Ind ction chemo

0 5 0 5

  • Induction chemo

0.5 0.5

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SLIDE 13

Impact of Induction Chemotherapy Impact of Induction Chemotherapy

No induction therapy

14 16

py Induction chemotherapy

8 10 12 2 4 6 8 2 Preop Hb (g/l) Blood transf. (units) Hosp stay (days) (units)

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SLIDE 14

Hemi Hemi-thoracic Radiation thoracic Radiation Hemi Hemi-thoracic Radiation thoracic Radiation

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SLIDE 15
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SLIDE 16

Hemithoracic Radiation (N=12) Hemithoracic Radiation (N=12)

5 6 7

Grade 1 Grade 2

3 4 5

Grade 3

1 2

Skin erythema Fatigue Nausea Eso- phagitis Vertigo

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SLIDE 17

Toronto Trimodality Therapy Update Toronto Trimodality Therapy Update

  • 2001 - December, 2007: 60 patients

– Induction chemotherapy: 50

  • Cisplatin + vinorelbine 26; pemetrexed 24; other 10

No resection: 15 – No resection: 15

  • Progressive disease:

4

  • Unresectable:

6 P iti di ti 5

  • Positive mediastinoscopy:

5

– EPP: 45

  • Operative mortality:

3 (7%)

– Adjuvant hemi-thoracic radiation: 30

  • 3-D conformal (54 Gy in 30 fractions)
  • IMRT (50 Gy in 25 fractions)

( y )

dePerrot, JCO; in press

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Complications of Trimodality Therapy Complications of Trimodality Therapy Complications of Trimodality Therapy Complications of Trimodality Therapy

Table 2. Severe adverse events recorded during the tri-modality therapy* Complications Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 Pulmonary emboli 3 1 Chemotherapy Surgery Radiation Pulmonary emboli 3 1 Leukopenia 1 Cardiac herniation 1 Cardiac arrhythmia 10 1 Bronchopleural fistula 1 1 Esophageal perforation 1 Esophageal perforation 1 Gastric herniation 1 Chylothorax 1 Fatigue 5 Nausea 1 * Severe adverse events defined by grade 3 to 5 toxicity according to the NCI CTCAE version 3.0 guidelines

dePerrot, JCO; in press

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SLIDE 19

Overall Survival Overall Survival Overall Survival Overall Survival

60 patients; median survival 14 months

80 90 100 40 50 60 70 80

urvival

10 20 30 40

Su

12 24 36 48 60 72

Time (months)

dePerrot, JCO; in press

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SLIDE 20

Survival According to Nodal Status and Survival According to Nodal Status and Therapy Therapy Therapy Therapy

dePerrot, JCO; in press

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SLIDE 21

Disease Disease-

  • free Survival in Patients Who

free Survival in Patients Who Completed Trimodality Therapy Completed Trimodality Therapy Completed Trimodality Therapy Completed Trimodality Therapy

N = 30

90 100

al

50 60 70 80

ree surviva

10 20 30 40

Disease-fr

12 24 36 48 60 72

Time (months)

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SLIDE 22

Toronto Trimodality Therapy Toronto Trimodality Therapy Toronto Trimodality Therapy Toronto Trimodality Therapy

  • Median survival

– Epithelial vs biphasic: 18 vs. 12 mo (p=0.002) – N 0 disease

  • Completed trimodality therapy vs incomplete
  • 59 vs. 8 mo (p=0.0001)

Ch i – Chemo regimen: ns

  • 5 year disease-free survival

– 53% in all N0 patients

  • 75% in T1-2
  • 45% in T3 4
  • 45% in T3-4
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SLIDE 23

Recurrance Following Trimodality Recurrance Following Trimodality Therapy Therapy Therapy Therapy

  • Recurrences

Recurrences

– 16/30 patients

  • Ipsilateral chest:

4 local ps ate a c est: local

  • Pericardium:

1

  • Peritoneum:

5 surgical seeding

  • Contralateral chest: 4

vs distant mets?

  • Chest and peritoneum: 2
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SLIDE 24

Tumour Seeding Tumour Seeding Tumour Seeding Tumour Seeding

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Neo Neo-adjuvant IMRT for Mesothelioma adjuvant IMRT for Mesothelioma Neo Neo-adjuvant IMRT for Mesothelioma adjuvant IMRT for Mesothelioma

Cho, dePerrot, Feld

  • Phase 2 study in 25 patients with cT1-2 N0

– Resectable patients only

  • 25 Gy in 5 fractions over 1 week

– 5 Gy boost to gross disease

  • EPP 1 week following XRT
  • Pathologic node negative > no treatment
  • Pathologic node positive > adjuvant chemo
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SLIDE 26

IMIG 2005

Low Low-

  • dose Computed Tomography For The

dose Computed Tomography For The l i i Of h li A d l i i Of h li A d Early Diagnosis Of Mesothelioma And Lung Early Diagnosis Of Mesothelioma And Lung Cancer In Prior Asbestos Workers: Cancer In Prior Asbestos Workers: P li i R l P li i R l Preliminary Results Preliminary Results

Michael R. Johnston, MD, FRCSC Heidi Roberts, MD

University of Toronto University Health Network Toronto, Ontario, Canada

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SLIDE 27

Methods Methods Methods Methods

  • Early detection study in a population at risk for

y y p p pleural mesothelioma

– Prevalence and incidence

  • Inclusion criteria

– History of asbestos exposure at least 20 years ago – Asbestos exposure with pleural plaques on chest x-ray

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SLIDE 28

Methods: follow up flow chart Methods: follow up flow chart

Baseline low-dose CT

Methods: follow up flow chart Methods: follow up flow chart

no or inconspicuous plaques

  • r

no or non-specific nodules indeterminate nodules

(≥5 mm solid or ≥8 mm non-solid)

  • r

suspicious plaques suspicious nodules (≥15 mm)

  • r mass-like plaques

with effusion endobronchial nodules no or non-specific nodules

lobulated, asymmetric, effusion

with effusion annual repeat 6 months f/u immediate biopsy 3 months f/u no change no change resolved (mucous) stable growth bi-annual repeat annual repeat annual repeat bronchoscopy biopsy etc.

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SLIDE 29

Update on Early Detection Study (9/08) Update on Early Detection Study (9/08) Update on Early Detection Study (9/08) Update on Early Detection Study (9/08)

  • 751 participants (98% male; average age 61)


– 84% with lung nodule (20% > 4mm; 1% GGO) – 62% with pleural plaques 2% ith l l ff i – 2% with pleural effusion

  • 14 cancers found

– 6 meso (3 pleural 3 peritoneal) 6 meso 
(3 pleural, 3 peritoneal) – 8 lung cancers 


  • Mesothelin and osteopontin assays are in progress

p y p g

  • Expanding endpoints to include asbestos related

lung disease

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SLIDE 30

Plasma markers in patients with MPM Plasma markers in patients with MPM Plasma markers in patients with MPM Plasma markers in patients with MPM

Prospective evaluation in patients with MPM (38) and asbestos exposed matched controls (64) asbestos exposed matched controls (64)

Anraku, IMIG; 2008

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SLIDE 31

Ketch Harbour, Nova Scotia