Physics contribution
Intensity-modulated radiation therapy: a novel approach to the management of malignant pleural mesothelioma

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Abstract

Purpose: Malignant pleural mesothelioma (MPM) causes symptoms and death mainly due to local progression, even after combined modality treatment. Poor local control after conventional radiotherapy may be due to the low dose of radiation that has been administered or to restriction of the target volume to avoid critical organs. Intensity-modulated radiation therapy (IMRT) has the potential to overcome these geometric/dosimetric constraints.

Methods and Materials: Seven patients with MPM who had an extrapleural pneumonectomy (EPP) were treated with adjuvant IMRT. The clinical target volume (CTV) included the surgically violated area inside the chest wall with particular attention to the insertion of the diaphragm, pleural reflections, and the deep margin of the thoracotomy incision. Treatment was delivered by intensity-modulated 6-MV photon beams using dynamic multileaf collimation.

Results: The CTV ranged from 2667 to 7286 mL. The average CTV covered to 50 Gy was 94% (range, 92% to 98%). Respiratory motion was minimal. The average volume of the boost areas covered by 60 Gy was 92% (range, 82% to 99%). Dose-volume constraints for normal tissue were met in almost all cases. Acute toxicity was mild to moderate. The most severe side effects were anorexia, nausea or vomiting, and dyspnea. Esophagitis was absent or mild. After a minimum of 13 months follow-up care there were no cases of disease recurrence within the ipsilateral hemithorax.

Conclusion: Treatment of the extensive operative area after an EPP is feasible using IMRT. Input from the radiologist and from the surgeon in the planning process facilitates definition of the high dose volumes. In light of patients’ tolerance to post-EPP IMRT, it may be feasible to incorporate systemic therapy, including novel biologic therapies into the treatment regimen.

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive malignancy in which local disease progression is the main cause of symptoms and death. Disseminated disease is seen only very late in the course of MPM 1, 2. MPM spreads by direct extension and seeding throughout the pleural space, including fissures, diaphragmatic and pericardial surfaces, through the chest wall, and into the mediastinum, peritoneum, and lymph nodes. The major problem for patients with MPM is poor local disease control in the thorax. Aggressive surgery alone, even in carefully selected patients, does not improve the 2-year survival rate of 10% to 33% 3, 4, 5. Although combined modality treatment has been reported to improve local control and survival rate 6, 7, 8, local recurrence is still the most common site of first relapse (9).

Even after extrapleural pneumonectomy (EPP), the diffuse nature of most malignant mesotheliomas and the manipulation of the exposed tumor during surgery puts the entire ipsilateral chest wall, diaphragm insertion, pericardium, mediastinum, and bronchial stump at very high risk of local recurrence. The hemithorax and mediastinum have an irregular shape and are adjacent to critical structures such as the spinal cord, liver, kidneys, esophagus, heart, and contralateral lung. Conventional radiotherapy to the hemithorax and mediastinum is limited by the ability of these organs to tolerate radiation 1, 9, 10 as well as by the total volume of tissue being irradiated.

Intensity-modulated radiation therapy (IMRT), however, has the potential to conform radiation doses tightly to target volumes. IMRT can reduce normal tissue toxicity, such as the parotid gland in head-and-neck neoplasms (11) and the rectum in prostate cancer (12), compared with standard techniques. In other disease sites with complex target volumes, IMRT generally results in superior dose distributions compared with those resulting from more traditional techniques.

In this study, we sought to determine whether IMRT after EPP might provide better target coverage than would traditional radiotherapeutic approaches. Because the definition of the target volume in postoperative radiotherapy of MPM has not been well described in the literature, techniques were also developed in close collaboration with thoracic surgeons to improve postoperative target definition. It was found that IMRT could be used to deliver 50 to 60 Gy to the hemithorax after EPP and that better than expected local disease control was thereby achieved. This is the initial experience with IMRT at The University of Texas M. D. Anderson Cancer Center. We here report the target volumes, dose distribution, toxicity effects, and patterns of time to disease recurrence and length of survival.

Section snippets

Patient data

Between June 2000 and February 2001, 7 patients with MPM underwent EPP. After giving informed consent, they were treated with adjuvant IMRT. Patient characteristics are shown in Table 1. All patients were men, though this was not part of the selection criteria. Their disease was staged using the two most common mesothelioma classification systems 13, 14, 15.

Patient selection, staging, and follow-up

Thoracic surgeons at M. D. Anderson Cancer Center identified potential candidates for the study. Eligible patients must have undergone EPP

Surgical findings

The features of the tumors found at surgery and upon pathologic examination are shown in Table 3. All of the tumors were quite extensive and often involved the chest wall or lung at multiple locations. Four of the 7 patients were found to have disease involving the lymph nodes.

Treatment planning and setup

In this group of patients, radiotherapy treatment planning required 3 to 8 weeks from the time of simulation to the first treatment. One patient required replanning because of an unavoidable 8-week delay from simulation

Discussion

The incidence of MPM in the United States is rising 17, 18, and is likely to continue to increase due to the 35- to 40-year lag between asbestos exposure and clinical presentation of the MPM 19, 20, 21. Other carcinogens such as the simian virus-40 also may play a role in MPM 22, 23, suggesting that the peak incidence of MPM may be many years away.

The prognosis for MPM has traditionally been dismal; the median length of survival is 4 to 12 months without intervention 24, 25, 26. In a

Conclusions

IMRT after EPP for MPM is feasible, and greatly facilitated by close interaction between the thoracic surgeon, radiation oncologist, and radiation physicist. Toxicity is modest, with the most serious side effects being fatigue and anorexia. Local control is excellent, with promising survival results at this early time.

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