New Era for Malignant Pleural Mesothelioma

Updates on Therapeutic Options

Anne S. Tsao, MD, MBA; Harvey I. Pass, MD; Andreas Rimner, MD; Aaron S. Mansfield, MD

Disclosures

J Clin Oncol. 2022;40(6):681-692. 

In This Article

Radiation Oncology

Radiotherapy (RT) plays an important role in the management of MPM and can be delivered in the adjuvant, neoadjuvant, and palliative settings. In early-stage resectable MPM, RT is typically delivered to the hemithorax before or after non–lung-sparing surgery (ie, EPP) or to the involved pleural space after lung-sparing surgery. Adjuvant conventionally fractionated hemithoracic RT after EPP to 54–60 Gy is safe and associated with low rates of locoregional recurrence.[51,52] Hence, it is recommended to use modern techniques (ie, 3D conformal RT, intensity-modulated radiotherapy, or proton therapy) to minimize radiation doses to surrounding normal tissues, especially the heart and contralateral lung.[53–55] A randomized trial on the use of hemithoracic RT following EPP closed early to accrual and thus did not meet its primary end point of locoregional relapse-free survival.[56] Its use should therefore remain limited to centers with significant experience in treating MPM with RT.

The Surgery for Mesothelioma after Radiation Therapy radiotherapy regimen, referenced earlier in the surgical section, consists of a short, neoadjuvant, hypofractionated course of hemithoracic intensity-modulated radiotherapy delivered to 5–6 Gy for five fractions followed by complete resection of the lung via EPP to avoid the development of radiation pneumonitis in the ipsilateral hemithorax. This multimodality treatment approach has resulted in impressive long-term disease control with a median survival of 24.4 months overall, but 42.8 months in a subset of patients with epithelioid MPM.[49,57,58] However, the 30-day perioperative grade 3–4 toxicity rate was 49%, indicating that this aggressive treatment approach should only be offered to appropriately selected patients at a tertiary care center with significant expertise in mesothelioma treatment.

Adjuvant hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after lung-sparing pleurectomy decortication to a total dose of 50–60 Gy in conventional fractionation is safe and feasible, as shown in multiple phase II studies.[59–61] Figure 2 illustrates the IMPRINT radiation fields after lung-sparing surgery. Arc therapy and proton therapy may further improve normal tissue dosimetry and target coverage.[62,63] A single-center phase III randomized trial comparing palliative RT with radical hemithoracic radiation therapy demonstrated an improvement in 2-year overall survival from 28% to 58%. NRG LU-006 (NCT04158141) is an ongoing cooperative group multicenter phase III randomized trial designed to evaluate the survival benefit of adjuvant IMPRINT using photon or proton therapy following lung-sparing surgery and systemic therapy.

Figure 2.

Right-sided hemithoracic intensity-modulated pleural radiation therapy plan to a total dose of 5,040 cGy in 28 fractions. The red line represents the planning target volume.

RT can be used for palliation of pain, eg, from tumor invasion into chest wall or spine, spinal cord compression, superior vena cava syndrome, and other obstructive symptoms. Some studies have described better response rates with fraction sizes of ≥ 4 Gy.[64] A prospective single-arm phase II study demonstrated 47% pain improvement with a relatively low dose of 20 Gy in five fractions.[65] A randomized study (SYSTEMS-2; ISRCTN12698107) is currently evaluating the palliative effect of higher doses of 36 Gy in six fractions.

Recurrences in the chest wall along prior diagnostic or therapeutic procedure tracks have been observed in patients with MPM. Therefore, prophylactic radiotherapy to prevent procedure-tract metastases was previously advocated based on initial promising data.[66,67] However, no consensus could be reached in several systematic reviews of this topic.[68,69] More recently, two large randomized trials showed no benefit of prophylactic radiotherapy to diagnostic or therapeutic procedure tracks. A multicenter, phase III, randomized controlled trial of 203 patients investigated immediate versus deferred radiotherapy (21 Gy in three fractions) to large-bore pleural intervention sites.[70] Although radiotherapy was well tolerated, there was no significant difference in development of procedure-tract metastases. Another even larger phase III, randomized trial of 375 patients compared prophylactic radiotherapy within 42 days of a procedure versus no radiotherapy.[71] This study also failed to detect a significant difference in the incidence of chest wall metastases at 6 months. Thus, there is no role for the routine use of prophylactic radiotherapy to prevent chest wall recurrences.

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