Combined Modality Treatment in Mesothelioma

A Systemic Literature Review With Treatment Recommendations

Charlotte De Bondt; Ioannis Psallidas; Paul E. Y. Van Schil; Jan P. van Meerbeeck


Transl Lung Cancer Res. 2018;7(5) 

In This Article

PICO 2: What Is the Optimal Regimen Within Each Modality?

What Is the Optimal PORT-technique?

RT of the pleura is understandably challenging as there is a large surface area to irradiate, the shape is complex and there are vital organs and large vascular structures close to the pleura that need to be shielded from radiation as much as possible.[33] The evolution towards lung sparing surgical techniques introduces additional difficulty as measures must be taken to avoid radiation pneumonitis or other complications in the spared ipsilateral as well as in the contralateral lung. The most frequently used radiation technique in multimodality treatment protocols for MPM are conventional 3-dimensional conformal RT and intensity modulated RT (IMRT). Conventional 3D hemithoracic RT has shown to be excessively toxic by Gupta et al. and Stahel et al. among others, both in the context of lung sparing surgery and after EPP.[22,34] IMRT allows for a tailored approach wherein large doses of radiation are administered to the affected pleura and the underlying lung and surrounding tissue are spared.[35] Helical tomotherapy or dynamic arc RT combines the precision of the IMRT technology with a megavoltage CT-scan. This allows for daily image-guided adjustments, which creates a more precise application of radiation. The fact that the radiation beam moves around the patient while the table moves through the arc enables irradiation of larger areas in a shorter time period.[36] Sylvestre et al. applied this technique for MPM in 24 MPM patients after EPP and reported a median disease free survival of 24 months. Two patients died of radiation pneumonitis.[36] Krayenbuehl et al. compared IMRT and 3D conformal RT in 39 MPM patients after EPP. They found a non-significantly longer median time to relapse in the IMRT group (16.2±3.1 versus 10.9±5.4 months with 3DRT). This did not however result in a longer overall survival (22.3±15.3 months for IMRT and 21.2±9.2 months for 3DCRT), probably because of a higher rate of distant relapse.[33] Rimner et al. evaluated IMRT after CT and P/D and reported a median progression free survival of 12.4 months and a very promising median overall survival of 23.7 months. There were no treatment related deaths. There were 8 cases (30% of patients) of grade 2–3 pneumonitis which responded well to steroid treatment.[35] In conclusion, IMRT techniques are hence likely to be preferable to 3DRT with regards to toxicity.

What Is the Optimal CT Regimen?

The standard CT regimen in multimodality treatment for MPM is a cisplatin-pemetrexed doublet. Pasello et al. performed a retrospective analysis of 51 patients who received neoadjuvant CT (pemetrexed plus cisplatin or carboplatin) as part of a multimodality treatment approach for MPM. Although they report a similar median progression free survival outcome in both groups (14.5 months in the carboplatin group versus 13.1 months in the cisplatin group), overall survival was significantly longer in the carboplatin group (25.5 versus 15.2 months in the cisplatin group). The authors attribute this to the patients' characteristics being more favorable in the carboplatin group. When they compared outcomes for only epithelioid-type mesothelioma in both groups, the difference was not statistically significant (26.9 months in the carboplatin group versus 18.9 months in the cisplatin group, P=0.054). As expected, cisplatin was tolerated more poorly and treatment with cisplatin resulted in higher numbers of anemia, nausea, vomiting and asthenia as opposed to carboplatin-based therapy.[37] A Turkish series, in which patients were treated with a pemetrexed-carboplatin doublet similarly showed a better median survival than with a pemetrexed-cisplatin doublet.[38]

In conclusion, these reports suggest that carboplatin containing regimens could be equally effective and less toxic and thus preferable in a combined modality approach already hampered by other toxicities.