Clinical case Pleural mesothelioma Francesco Lucio
Malignat Pleural Mesothelioma Mesothelioma is a rare malignant tumour originating from the cells lining the mesothelial surface of the coelomic cavities of the body. The background incidence of MPM is very low. Asbestos is the principal etiological agent of MPM. The first studies on the association between asbestos and MPM were published in the 1960s. Since most asbestos exposure is workrelated, mesothelioma is an occupational disease in the majority of cases J.P. van Meerbeeck et al. / Critical Reviews in Oncology/Hematology 78 (2011) 92 111
Consumo di amianto pro capite (Tonnnellate per milione di ab.) Numero annuale di decessi Consumo di amianto (1915-1992) e decessi 1 per mesotelioma osservati 2 (1970-1999) e previsti (2000-2030) in Italia 3000 2500 2000 1500 1000 500 0 1992 1987 1982 1977 1972 1967 1962 1957 1952 1947 1942 1937 1932 1927 1922 1917 1912 FABIO MONTANARO 1, ALESSANDRO MARINACCIO2 et al. Anno in cui l'amianto è stato proibito 1992 Anno 40-45 anni* Atteso 2017 2027 2022 2017 2012 2007 2002 1997 900 800 700 600 500 400 300 200 100 0 Stima 1 picco 2017: 820-940 MM per anno Consumo procapite Ossevati Proiezione Media Mobile su 5 per. (Ossevati) Media Mobile su 5 per. (Consumo procapite) 1 Peto et al *Selikoff IARC Scientific Publication 1 Uomini, 25-89 anni 1977 2 Stimati: decessi per tumore pleurico * 0.73
Terapia dei Mesoteliomi Nessuna terapia (supporto) Radioterapia esclusiva Pleurectomia/Decorticazion e P/D + RT postoperatoria PleuroPneumonEctomia/PP E PPE + RT postoperatoria +/- CT + + +
Radiotherapy in MPM Palliative radiotherapy: for palliation of symptoms for patients with advanced disease As for other palliative indications,hypofractionation with 4G fractions is currently advocated, for a total dose bio-equivalence of 30 36 Gy. Prophylactic radiotherapy to reduce recurrences at sites of diagnostic or therapeutic instrument insertion irradiation with a 7 Gray (Gy) fractionation for three consecutive days, in the four weeks Postoperative/Radical Treatment RT as part of multimodal definitive treatment to improve locoregional control after resection of early stage disease total dose more than 54 Gy to the hemithorax. The use of radiation therapy to the full hemithorax is limited by critical organs (lung, liver, heart, spinal cord, esophagus and Kidney).
Radiotherapy ESOPHAGUS CONTROLATERAL LUNG CONTROLATERAL KIDNEY STOMACH PTV IPSLATERAL KIDNEY SPINE Large irregularly shaped area at risk Proximity of critical structures
3D CRT Moderate dose radiotherapy MDRT AP/PA 30 Gy The mediastinum was treated to an additional 10 Gy for a cumulative dose of 40 Gy. A. M. ALLEN et al.2007
3D CRT High Dose RT A. M. ALLEN et al.2007 AP/PA 39.6 Gy Abdominal block to shield kifney and partial liver- area treat with electrons. AP/PA off cord to block spine and mediastinum. Heart block eventually for left lung Boost 14.4 Gy e - e-
ADJUVANT MALIGNANT MESOTHELIOMA RADIOTHERAPY: HOW MANY DIFFICULTIES! Russi, Lucio et al IJROBP 2006
3D CRT moderate vs high radiotherapy A. M. ALLEN et al.2007 It suggested that a greater radiation dose and a larger volume to include the entire hemithorax and adjacent areas could perhaps reduce the locoregional failure rate
Quale Bersaglio? 65% P/D Flores 11% 30% EPP 22% 21% P/D Pleurectomia/decortica zione [P/D] rimuove la pleura e il mesotelioma senza rimuovere il polmone. 39% EPP PleuroPneumonEctomia rimozione di: Polmone Pleura parietale e viscerale Diaframma Pericardio Flores 08
3D CRT vs IMRT PTV1 45Gy PTV2 56-57Gy KRAYENBUEHL et al, Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 5, pp. 1593 1599, 2007
3D CRT vs IMRT IMRT seems to be the superior technique to deliver greater doses with better dose homogeneity, even though the larger doses to the OARs, especially in the contralateral lung, must be taken into consideration KRAYENBUEHL et al, Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 5, pp. 1593 1599, 2007
IMRT vs tomotherapy Target homogeneity and coverage could be significantly improved with tomotherapy
IMRT vs tomotherapy slight advantages in normal tissue sparing
IMRT vs RA RA demonstrated similar target coverage and better dose sparing to the OARs compared with fixed-gantry IMRT. The time required to deliver the dose was much lower M. SCORSETTI et al. 2010
WARNING Fatal Radiation Pneumonitis Conventional RT N of pts % of Fatal RP Toronto General Hospital 29 0% University of Padua 15 0% MSKCC 54 0% BWH 183 0% IMRT N of pts % of Fatal RP Allen, BWH 06 13 46% NKI, Denmark 08 26 15% Miles, Duke 08 13 8% Rice, MDACC 07 63 10% Gupta et al. 2009
WARNING New DVH for controlateral lung Study DVHs for controlateral lung MLD V20 Allen, BWH 06 > 13 Gy > 15% Miles, Duke 08 > 11 Gy > 7% Rice, MDACC 07 > 8.5 Gy > 7% most frequent side effects ipsilateral kidney is largely included in the radiation field, contralateral kidney should in fact contribute to the entire renal perfusion
Clinical Case Patient Profile Uomo 30/1/51 59 anni Esposizione professionale all amianto 25/5/2010 biopsia pleurica 22/6/2010 chirurgia mediastino scopia cervicale 6/7/10 pleuropneumectomia istologico pt1bpn0
IMRT 11/11/2010 inizio PORT 1.8 Gy x 27 sed = 48.6Gy S&S 7 beams 83 segments 46 Gy
CI95=0.16 HImax=1.16 DVH D98=44.7Gy D50=48.5Gy V5=30% MLD =5Gy V20=2.5% D2=51.8Gy
Pre-treatment dosimetry Gamma(4% 3mm)= 96.5% Omnipro with EBT in CIRS phantom
PET CT 8/6/2012 2010 Captazione pleurica 2012
Conclusion
Conclusion The most appropriate timing should be discussed upfront in a multidisciplinary board, including radiation oncologists. Dose of radiation for adjuvant treatment following EPP should be 50 54 Gy in 1.8 2 Gy daily fractions, with 60 Gy delivered to macroscopic residual tumors if any. IMRT is a promising treatment technique reduce radiation exposure of the remaining lung, as the risk of fatal pneumonitis with IMRT (V20 < 10%; mean lung dose preferably <8.5 Gy; low dose volumes minimized, with V5 < 60%).