Integration of Radiation Therapy Into MuIti-modality Mesothelioma

Integration of Radiation Therapy 

MPM remains a therapeutic challenge with a poor prognosis. Many patients present with advanced disease, have numerous comorbidities or poor performance status, and are therefore only eligible for best supportive care and palliative management. For those who are diagnosed at an operable stage, a multimodality approach of chemotherapy, surgery, and radiation therapy is commonly applied. 

The combination of all the three treatment modalid.es carries a significant risk for toxicity for the patients and calls for sophisticated treatment planning in high-volume medical centers with experience in treating the disease given the challenging and complex nature of MPM.

Two types of surgical resection have been most commonly used in the management of resectable MPM. An extrapleural pneumonectomy (EPP) is the most comprehensive radical surgery and involves an en bloc resection of the lung, pleura, pericardium, and diaphragm. 

Somewhat surprisingly, even after such an extensive surgery as an EPP, up to 80% of patients still experience local intrathoracic recurrence indicating that additional adjuvant therapy may be needed to reduce the significant risk of local recurrence. In addition, EPP is associated with significant morbidity and mortality, thus being applicable to only a subset of patients with excellent functional status and operability.

A less complete resection but an alternative associated with lesser morbidity and mortality is a lung-sparing pleurectomy/decortication (P/D) which involves resection of the parietal and visceral pleura, with or without resection of the pericardium and diaphragm while the lung is spared. Given that P/D is a less comprehensive oncologic surgery and by default is assumed to leave microscopic cells behind, the case for adjuvant therapy is even stronger.

Somewhat surprisingly early retrospective comparisons of EPP and P/D revealed higher morbidity, decreased quality of life (QOL), and worse overall survival with EPP when compared to P/D (Flores et al. 2008). The Mesothelioma and Radical Surgery (MARS) trial were designed to prospectively assess the feasibility to randomize patients to EPP versus no EPP after induction chemotherapy (Treasure et al. 2011). 

Fifty patients were randomly assigned, and with a median survival of 14.4 months in randomly assigned patients, there were no significant differences in survival between patients undergoing EPP compared to NOB. However, this trial was not designed or fed for an end to survival and has been very criticized for multiple reasons, including its high mortality rate in patients who underwent EPP (18%). 

A great meta-analysis of 1512 patients undergoing a P/D and 1391 subjected to EPP confirmed the finding of a worse survival after EPP (Taioli et al. 2015). Taken together, these studies have led to greater use of P/D in the surgical management of MPM. However, EPP can still have a role in the surgical treatment of MPM, that is, in particularly tight patients whose tumors cannot be eliminated without a pneumonectomy.

The majority of experts in Mesothelioma will agree that, regardless of what surgical technique is used, complete macroscopic resection (MCR) is the objective of cytoreductive surgery in patients with MPM and has been associated with favorable results in properly selected patients properly selected (Rice et al. 2011). The choice of approach and surgical technique depends on the presentation of the individual patient, the extension of the tumor, and medical aptitude and should be applied highly individualized.

Given the high risk of disease progression, even in patients with early MPM, surgical resection has been typically used as part of a multimodality treatment approach, combined with systemic or intrapleural chemotherapy, RT 3D 3D 3D pre o post-o post-operative -Modulated radiotherapy (IMRT). In this chapter, we will describe the radiotherapy options that can be used in the EPP and P/D environment, as well as other indications beyond patients who are surgical candidates.

For a long time, it was believed that RT to the entire hemithorax would not be feasible, since the large field necessary to treat the entire pleura would be too toxic. This was first attempted in patients who had undergone extrapleural pneumonectomy (EPP), as the EPP completely removed the lung on the fully involved hermit thoracic side which thus no longer had the potentially life-threatening inflammation from radiation therapy. 

At first, conventional photon/electron technology was used to target hemithorax, block at-risk abdominal organs and the heart for left-sided tumors, and supplement RT doses to anterior and posterior thoracic guardians with electron fields (Yajnik et al. 2003). One advantage of this approach is the avoidance of oblique angles that would increase counter-lateral lung exposure to ionizing radiation and the risk of radiation pneumonitis.

Source

Harvey I. Pass, Nicholas Vogelzang, Michele Carbone - Malignant Mesothelioma_ Pathogenesis, Diagnosis, and Translational Therapies-Springer (2005)

Mary Hesdorffer, Gleneara E. Bates-Pappas - Caring for Patients with Mesothelioma_ Principles and Guidelines-Springer International Publishing (2019)

Bruce W S Robinson, A Philippe Chahinian - Mesothelioma (2002).

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