Radiation Therapy for Malignant Pleural Mesothelioma
Treatment of malignant pleural mesothelioma with radiation therapy (RT) is extremely challenging. The target volume for treatment is very large, involving almost the entire hemithorax, and within and adjacent to this treatment volume, there are many normal structures with low tolerances to radiation. Consequently, it is very difficult to create treatment plans that deliver satisfactorily high doses to the complex target volume yet minimal doses to the adjacent radiosensitive normal organs. This chapter will review the history, current approaches, and future ideas for the treatment of pleural mesothelioma with radiotherapy in definitive, adjuvant, and palliative settings.
Definitive Radiation Therapy Alone for Mesothelioma
For the treatment of unresected gross disease, the target volume for RT includes the entire visceral and parietal pleura of one lung. These structures form a circumferential envelope around the lung, extend along fissures between lobes of the lung, and are attached to ipsilateral, pericardial, and diaphragmatic surfaces. A tumoricidal dose of RT for gross disease is >60 Gy, but the normal tissue tolerance of the adjacent organs is much lower. Whole organ tolerances for these structures are as follows: lung, 18 to 20 Gy; heart, 40 Gy; liver, 30 Gy; stomach, 50 Gy; kidney, 18 to 20 Gy; spinal cord, 45 to 50 Gy; and brachial plexus, 50 Gy.1
Few reported series address the definitive treatment of unresected pleural mesothelioma, and none show promising results. In 1988, Alberts et al.2 reported outcome for 262 patients treated with various combinations of RT, pleurectomy, and chemotherapy. RT was delivered to the entire hemithorax with doses of 45 to 80 Gy. All treatment groups had similar outcomes, with a median survival time of 9.6 months; the stepwise addition of treatment modalities was not associated with improved survival. No toxicity data were described. The authors concluded that new agents and approaches were warranted.
In 1990, Ball and Cruickshank3 reported on a series of 35 patients treated with RT at the Peter MacCallum Institute, 12 of whom received “radical RT.” Treatment comprised 40 Gy to the entire hemithorax using AP–PA fields, after which the spinal cord was blocked and the treatment continued to a total dose of 50 Gy. An anterior cardiac block was used for left-sided tumors to limit heart dose to 40 Gy; no shielding was used for lung, liver, or kidney. There were two treatment-related fatalities (17%) due to radiation hepatitis and radiation myelopathy, respectively. Median survival time was 9 months. The authors concluded that there is no role for radical RT given the unacceptable toxicity and lack of demonstrated efficacy.
A third report by Maasilta4 in 1991, included 34 patients with unresected mesothelioma who were treated to the entire hemithorax with three different high-dose regimens. The spinal cord was shielded after 40 Gy, the liver was partially shielded after 30 Gy, and there ...