·         Staging IMIG (International mesothelioma interest group classification)

o        Stage 1 : Confined to capsule of parietal pleura, lung, pericardium or diaphragm

o        Stage 2 : As above with N1 or N2 station nodes

o        Stage 3 : Local extension into chest wall, mediastinum, heart, through diaphragm, peritoneum, with or without nodal involvement

o        Stage 4 : Distant metastases

·         Pathology

o        Associated with asbestos exposure (check history), esp Chrysotile and rod like amphibole asbestos. SV40 DNA present in 60% of mesotheliomas > tumour suppressor gene

o        Histology : Epithelioid, sarcomatoid, or mixed. 80% epithelioid 20% sarcomatous

o        Keratin +ve, Should be negative for CEA, AUA1 and BER-EP4 (which are positive in adenocarcinoma). TTF1 negative (cf lung cancers)

o        EM shows long thin microvilli as opposed to short thick microvilli in adenocarcinoma

·         Radical treatment

o        Sugarbaker series, highly selected patients treated with pleuropneumonectomy, chemo and RT to dose of 50Gy > 38% 5YS 15% 2YS

o        Still no RCT’s for radical therapy

·         Port site irradiation. Boutin et al > giving 21Gy in 3# over one week reduces risk of port site recurrence from 40% to nearly zero, but must give within 3/52 of procedure.

·         Very important to try and gain control of effusions, either by medical or surgical means

·         Palliative RT. Symptomatic benefit in 50% if cases, give 36Gy in 12# if good PS, or 10Gy single if poor PS

·         MS01 study :           Takes over from Meso-1 pilot

Active symptom control vs

ASC + MVP x 4 vs

ASC + Navelbine Carbo 6 weeks on, 2 weeks off, 6 weeks on

Must treat all symptomatic effusions before recruiting, need to do CT within a month of randomisation, need to do CT within a month of randomisation

·         Permetrexed            Multitargeted antifolate (DHFR and TS, so works like MTX & 5FU)

Good phase 2 results in mesothelio