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Malignant Pleural Mesothelioma MPM
Kinan Malek JalloulThoracic surgeon
5/7/2019
Malignant Pleural Mesothelioma MPM
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
Malignant Pleural Mesothelioma MPM
How Does Mesothelioma Develop?
Malignant Pleural Mesothelioma MPM
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%
Malignant Pleural Mesothelioma MPM
Staging
T1,2,3Stage I N0
Malignant Pleural Mesothelioma MPM
“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
Rice D et al.J Thorac Oncol 2011; 6:1304-12
Malignant Pleural Mesothelioma MPM
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
Malignant Pleural Mesothelioma MPM
vPD
resiction parietal+visceral pleura
without diaphragm&pericardiumall gross tumour to be removed
Rice D et al.J Thorac Oncol 2011; 6:1304-12
Malignant Pleural Mesothelioma MPM
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
Malignant Pleural Mesothelioma MPM
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
Rusch VW et al. J Thorac Oncol 2012;7:1631-9
Stage-Sur III EPP III PD IV EPP IV PDMST 16 19 12 15
Malignant Pleural Mesothelioma MPM
surgery only vs multimodality therapy
MSTSurgery+other 20
Rusch VW et al. J Thorac Oncol 2012;7:1631-9
Surgery+other 20 Surgery alone 11
Malignant Pleural Mesothelioma MPM
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)
Malignant Pleural Mesothelioma MPM
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
Malignant Pleural Mesothelioma MPM
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
Malignant Pleural Mesothelioma MPM
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
Malignant Pleural Mesothelioma MPM
6) several treatments together difference between living
few mos or more years
7) IMRT is now part of the care for almost all pts
Malignant Pleural Mesothelioma MPM
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