Malignant Pleural Mesothelioma MPMsta-sy.com/files/presentations/MPM_Kinan_Jalloul.pdf · Malignant Pleural Mesothelioma MPM vvery rare only 3,000 cases/y (USA) v75 percent of all

Malignant Pleural Mesothelioma MPM

Kinan Malek JalloulThoracic surgeon

5/7/2019


vvery rare only 3,000 cases/y (USA)v75 percent of all mesothelioma

Facts and Statistics

v75 percent of all mesothelioma vMost cases occupational exposurevage 50 to 70 yov20 to 50 y after being exposed to asbestosv>80% Mens

Malignant Pleural Mesothelioma MPM Asbestos

vAsbestos is the only known causevNaturally fibrous minerals in rocks and soil

Before the 1980 asbestos in over 5,000 consumer vBefore the 1980 asbestos in over 5,000 consumer products:construction materials - cement wallboardiroofing materials - fire resistant clothes


How Does Mesothelioma Develop?


vSymptoms: SOB-Chest Pain-Cough-HemoptysisWeight Loss - Fever or Sweating

vDiagnosis: Biopsies-CXR-CT-PET- MRIvDiagnosis: Biopsies-CXR-CT-PET- MRI

Biomarkers: fibulin-3, CA125, osteopontin

soluble mesothelin-related peptides (SMRP)

Malignant Pleural Mesothelioma MPMHistology

Epithelioid 50-70%

Sarcomatoid 10-20%

Biphasic(mixed) 30%


Staging

T1,2,3Stage I N0


“You need to treat the patient and not just the stage of the disease.”

“You need to treat the patient and not just the stage of the disease.”

Dr R.Flores

Malignant Pleural Mesothelioma MPMTreatmentvSurgery vChemotherapyvRadiationvRadiationvImmunotherapyvPhotodynamicvVirotherapyvGene TherapyvHormone Therapy

Emerging Treatments

Malignant Pleural Mesothelioma MPMSurgery - IndicationsESMO Guidelines (EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY)

§ Palliation of pleural effusions when chest tube drainage is not successful.not successful.

§ Diagnostic & staging.§ Part of a multimodality treatment, preferably as part of a

study.§ Perform a macroscopic complete resection by means of

P/D or EPP.Baas P et al. Ann Oncol 2015;26 suppl.5: v31-9

Malignant Pleural Mesothelioma MPMSurgery IASLC/IMIG consensus report 2011

vExtrapleural Pneumonectomy EPP

Extended Pleurectomy/DecorticationEPDvExtended Pleurectomy/DecorticationEPDvPleurectomy/Decortication P/D

vPartial pleurectomy

Rice D et al.J Thorac Oncol 2011; 6:1304-12

Curative intent

Diagnostic-palliative

Malignant Pleural Mesothelioma MPMSurgeryq Extrapleural Pneumonectomy (EPP)

En bloc resection pariatal+visceralpariatal+visceral

+ipsilateral lung+pericardium+diaphragm



vEPDresiction parietal+visceral pleura+diaphragm and/or pericardium+diaphragm and/or pericardiumall gross tumour to be removed

Rice D et al.J Thorac Oncol 2011; 6:1304-12 EPD


vPD

resiction parietal+visceral pleura

without diaphragm&pericardiumall gross tumour to be removed



systematic review of surgical treatments for MPMüoutcomes of EPD - EPP in a multimodality settingümeta-analysis (7 studies )

EPP EPD

Christopher Cao et al. Lung Cancer 2014;83:240-5

EPP EPD

nMortality

Morbidity

MST

632 513

6.8% 2.9%

62% 27.9%

12-22 mos 13-29 mos

Nakas A et al. J Euro Cardio-Thorac Sur2014;46:380-5


Initial analysis of IASLC MPM database

§ 3,101 pts - 15 centers - 4 continents§ Median age 63 years - 79% men - 62.3% epithelioid.§ (bTNM) stages : I (11%), II, (21%), III (48%), and IV (20%). § (bTNM) stages : I (11%), II, (21%), III (48%), and IV (20%). § Curative-intent surgery in 1494 patients (64.5%).

§ MST cTNM = pTNM: stage I 21 mosII 19III 16IV 12

Rusch VW et al. J Thorac Oncol 2012;7:1631-9

Malignant Pleural Mesothelioma MPMEPP vs P/D , Stage

Stage-Sur I EPP I PD II EPP II PDMST/mos 40 23 23 20


Stage-Sur III EPP III PD IV EPP IV PDMST 16 19 12 15


surgery only vs multimodality therapy

MSTSurgery+other 20


Surgery+other 20 Surgery alone 11


MARS 2 trial /Mesothelioma and Radical Surgery 2 trial/

• Started may/2015 - UK• Multicentre Randomised Trial • Multicentre Randomised Trial • Comparing EPD Versus no surgery• 2 cycles chemotherapy then repeat ct and pts

get randomised to either EPD oranother 4 cycles chemotherapy

Malignant Pleural Mesothelioma MPMChemotherapy § Types: Neoadjuvant - Intraoperative - Adjuvant

§ Alimta + Cisplatin + Avastin è increase 2.7 mos to OS /NCCN/

§ Delivery Methods: IV – Port – Oral( only in clinical trials)

§ Dr R.Flores published a study

IOCT after EPP===>MST=33 mos

Alimta (pemetrexed)https://www.mesotheliomaguide.com/treatment/chemotherapy/

Avastin (Bevacizumab)


Radiation/Indications

1. Hemithoracic RT befor or after EPP

2. Hemithoracic RT after PD2. Hemithoracic RT after PD

3. Palliative radiation for focal symptoms caused

by the disease

Daniel R. Gomez et al. J Thorac Oncol 2019;14:1172-83


RadiationqIORT /Intraoperative Radiation Therapy/ for PD pts:

one large dose of radiationqSMART/Surgery for Mesothelioma After Radiation Therapy/

Intensity Modulated Radiation Therapy (IMRT)Intensity Modulated Radiation Therapy (IMRT)prior EPP large doses of radiation 5 days prior to surgery.

q IMPRINT / Intensity Modulated Pleural Radiation Therapy/ after PD

https://www.cancer.org/cancer/malignant-mesothelioma/treating/radiation.html

Malignant Pleural Mesothelioma MPM• IMRT after EPP=== 2y OS 32%• MSKCC and MDACC :27 pts with

IMPRINT (46.8Gy) after CT and P/D è6pts g2 RP 2 pts g3 RP 0 pts g4,5 RP6pts g2 RP 2 pts g3 RP 0 pts g4,5 RP

2 years OS = 59%• Study IMRT vs conventional RT

Rosenzweig, K, “Malignant pleural mesothelioma: adjuvant therapy with radiation therapy”, June 2017, Annals of Translational Medicine, pp. 242

IMRT Conv RTesophagitis

MST23%20.2

47%12.3

Malignant Pleural Mesothelioma MPMImmunotherapy

ü3 Types: Cancer Vaccines-Checkpoint Inhibitors-Monoclonal Antibodies

ü currently in clinical trialsü stimulate immune systemü low side effects.

üPD-1 inhibitors nivolumab and Pembrolizumab

üCTLA-4 inhibitor Ipilimumab

https://www.cancer.org/cancer/malignant-mesothelioma/treating/immunotherapy.html

1 2 3

Malignant Pleural Mesothelioma MPMPhotodynamic PDTv IV photosensitizing agents 1 to 3 days prior to Laser applied to the tumour site.v Photofrin is the only FDA-approved

vIOPDT + PDJ.Friedberg/University of Pennsylvania in 2012 J.Friedberg/University of Pennsylvania in 2012

38 pts 97% Stage III or IV

http://www.annalscts.com/article/view/1214/1605

epithelioid nonepithelioid N2 Ø N2

MST 41.2 mos 6.8 31.7 57.1

Malignant Pleural Mesothelioma MPMvirotherapyØ Vaccinia – Herpes - MeaslesØ Oncolytic viruses naturally occurring or genetically engineeredØ Stimulate different types of immune

ØPhase II trial in UKØPhase II trial in UK27 pts with Stage III-IVTroVax® vaccine + Alimta + Cisplatin

showed robust immune activity, acceptable safety and tolerability

https://www.tandfonline.com/doi/abs/10.1080/2162402X.2018.1457597?journalCode=koni20&

summary

1) MPM survival rates are steadily improving

2) Surgery role: Diagnosis- staging- palliative- treatment


2) Surgery role: Diagnosis- staging- palliative- treatment

3) Multimodal therapy is the most successful type of treatment

4) Multimodal treatment plan is possible regardless of MPM

type or stage.

5) Many centers have limited their use of EPP in favor of P/D

6) several treatments together èdifference between living


6) several treatments together difference between living

few mos or more years

7) IMRT is now part of the care for almost all pts


ThanksThanks

Documents

Malignant Pleural Mesothelioma MPMsta-sy.com/files/presentations/MPM_Kinan_Jalloul.pdf · Malignant Pleural Mesothelioma MPM vvery rare only 3,000 cases/y (USA) v75 percent of all